Potential for Control of Harmful Cyanobacterial Blooms Using Biologically Derived Substances: Problems and Prospects

Journal of Environmental Management 125 (2013) 149e155

Contents lists available at SciVerse ScienceDirect

Journal of Environmental Management

journal homepage: www.elsevier.com/locate/jenvman

Review Potential for control of harmful cyanobacterial blooms using biologically derived substances: Problems and prospects

Jihai Shao a,b, Renhui Li c, Joe Eugene Lepo d, Ji-Dong Gu b,e,* a College of Resources and Environment, Hunan Agricultural University, Changsha 410128, PR China b Hunan Provincial Key Laboratory of Farmland Pollution Control and Agricultural Resources Use, Hunan Agricultural University, Changsha 410128, PR China c Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, PR China d Department of Biology, and Center for Environmental Diagnostics and Bioremediation, University of West Florida, FL 32514, USA e Laboratory of Environmental Microbiology and Toxicology, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China article info abstract

Article history: Water blooms of cyanobacteria have posed a worldwide environmental threat and a human health Received 22 May 2012 hazard in recent decades. Many biologically derived (but non-antibiotic) bioactive substances are known Received in revised form to inhibit the growth of aquatic bloom-forming cyanobacteria. Some of these biologically derived sub- 23 March 2013 stances (BDSs) have no or low toxicity to aquatic animals and humans. Most BDSs are easily biode- Accepted 3 April 2013 gradable in aquatic environments. These characteristics indicate that they may have potential for control Available online 6 May 2013 and removal of harmful algae. However, BDSs also have the disadvantages of high cost of preparation, and possible damage to non-target aquatic organisms, and sometimes, low efﬁciency of algae removal. Keywords: Cyanobacteria The ecological risks of most BDSs are still unknown. Here, we review recent research progress relative to Water blooms the inhibitory effects of BDSs on cyanobacteria, and critically analyze the potential of BDSs as algicides Biologically originated substances with an emphasis on possible problems during the process of controlling harmful cyanobacteria. We Algae removal suggest avenues of study to enhance effective use of BDSs in controlling of cyanobacterial blooms; these include guidelines for isolation and characterization of new effective BDSs, exploiting the synergistic effects of BDSs, the merits of controlling harmful cyanobacteria at the early stages of proliferation and evaluation of ecological risks of BDSs. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction Chemical approaches can effectively and rapidly remove algal blooms; however some algicidal chemicals such as CuSO4 and Eutrophication is a widespread problem in aquatic ecosystems herbicides can cause secondary pollution of aquatic environments around the world due to sewage and surface run-off. Cyanobacte- (Jancula and Marsálek, 2011). Moreover, the inhibitory effects of rial blooms can cause severe water quality deterioration including most algicidal chemicals do not selectively target harmful cyano- scum formation, toxin production, hypoxia, bad taste and odors bacteria; thus, non-harmful algae or beneficial organisms may also (Lopez et al., 2008). Cyanobacterial blooms can also lead to accu- be eliminated or negatively affected by chemical application and mulation of cyanotoxins in aquatic animals, and eventually, pose exposure. Introduction of concentrated chemical algicides into high risk to human health. Therefore, the removal of harmful cya- water bodies often leads to the collapse of aquatic ecosystems. nobacterial blooms is a crucial step for the maintenance of safe Physical approaches, such as mixing lake waters using an air water supplies and for the safety of aquatic products. Basically, compressor, ultrasonic damage to algal cells, pressure devices to there are three short-term approaches to eliminate or control collapse cyanobacterial gas vesicles, are also proposed to control harmful algal blooms (HABs): chemical approaches, physical ap- algal blooms (Visser et al., 2005). Compared with chemical ma- proaches and biological approaches (Anderson, 1997). Each of these nipulations, less subsequent secondary pollution is the most has advantages and disadvantages when applied to control of HABs. apparent merit of physical approaches in the removal of algae. But physical treatments of algae removal are energy intensive and tend to be of low efficiency (Gao and Xie, 2011). Moreover, injury to * Corresponding author. Laboratory of Environmental Microbiology and Toxi- non-target organisms by many energy intensive treatments in cology, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, fi Hong Kong, China. Tel.: þ852 2299 0605; fax: þ852 2559 9114. water also limits the eld application of such approaches in large E-mail addresses: [email protected] (J. Shao), [email protected] (J.-D. Gu). scale.

Biological approaches tend to be environmentally friendly and agricultural byproducts, such as brown-rotted wood (Pillinger et al., promising methods for controlling toxic cyanobacteria and HABs. 1995), deciduous leaf litter and coniferous leaf litter (Ridge et al., However, the efficiency of biological strategy is influenced by many 1995), rice straw and rice hull (Park et al., 2006, 2009), extracts of biotic and abiotic factors in the environment. Biological manipu- citrus peels (Liang et al., 2010), and wheat bran leachate (Shao et al., lations may effectively remove/control harmful cyanobacterial 2010) were shown to inhibit the growth of cyanobacteria. Among blooms in one water body but have no effect in another. Such them, barley straw has received the most extensive study. Bioassays variation in efficacy of algal removal discourages field application indicated that a wide range of algae, including cyanobacteria and using biological agents. eukaryotic algae, were susceptible to decomposing barley straw. Some non-antibiotic BDSs inhibit the growth of aquatic bloom- The typical bloom-forming and microcystins-producing genus forming cyanobacteria (Ridge and Barrett, 1992; Schrader et al., Microcystis aeruginosa was most susceptible to decomposing barley 1998; Nakai et al., 2000). These substances are currently classified straw (Martin and Ridge, 1999), which implies that it will be very into two groups: extracts of plants and identified natural chemicals useful for controlling of M. aeruginosa based blooms. from plants and microorganisms. Some of these BDSs, e.g., extracts of Ephedra equisetina root, L-lysine, may present little or no toxicity 2.2. Identified antialgal chemicals from plants and microorganisms to aquatic animals and humans (Yan et al., 2012; Kaya and Sano, 1996). Most of these BDSs are readily biodegraded in natural en- Identification of natural antialgal chemicals from plants and vironments. Some biological remediation agents exhibit selective microorganisms has been the main approach toward explaining inhibitory effects on cyanobacteria (Schrader et al., 2003). Taken inhibitory effects of those biological substances against algae. Many together, these qualities indicate that BDSs have great potential for antialgal chemicals (see supplementary material) have been iden- mitigation of cyanobacterial blooms. However, actual field appli- tified from plants and algicidal bacteria. The identified natural cations of BDSs to control harmful cyanobacteria are currently very antialgal chemicals are mainly phenols, quinones, alkaloids, organic limited due to some disadvantages of BDSs. Except for BDSs from acids, amino acid, terpenes and others. The 50% growth inhibitory extracts of some agricultural byproducts, high cost of algicide concentration (IC50) for compounds, such as Tellimagrandin Ⅱ preparation is the main disadvantage that discourages broad field (1,2,3-tri-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-b-D-glucose), applications of many identified natural antialgal chemicals (Jancula pyrogallic acid, ethyl 2-methylacetoacetate, nonanoic acid, salicylic and Marsálek, 2011). Compared with traditional algicidal chemicals acid, a-ionone, anthraquinone, naphthoquinone, sanguinarine, L-2- like CuSO4, low algae-removal efficiency is another disadvantage azetidinecarboxylic acid, b-sitosterol-b-D-glucoside, dicyclohexanyl for some BDSs. The action modes and ecological risks for most BDSs orizane, and berberine, were all less than 1 mg/L. Anthraquinone are still not fully understood. These factors all discourage further showed the strongest inhibitory effect against cyanobacteria with application of BDSs for control of cyanobacteria in aquatic envi- an IC50 of 0.016 mg/L. The lowest observed effect concentration ronments. In this paper, we critically analyze the inhibitory char- (LOEC) for quinones (2,3-dichloronaphthoquinone, 2-methylanthr- acteristics and inhibitory mechanisms of BDSs on cyanobacteria, aquinone, juglone), alkaloids (indole, L-2-azetidinecarboxylic acid, and the possible problems using BDSs for cyanobacteria control. On nostocarboline) and trans-cinnamic acid were all less than 0.03 mg/ that basis, we propose guidelines for the further study of BDSs and L. However, one should keep in mind that the data on effective their application in cyanobacterial control. concentrations against cyanobacteria in literature are not comparable. The target cyanobacteria used in the bioassay of those natural 2. Antialgal substances originated from biology chemicals differed, and different species and strains of cyanobacteria often exhibit dramatically different responses to one com- 2.1. Antialgal extracts of plants pound. For example, the IC50 of tryptamine against M. aeruginosa was 1.05 mg/L, while, it was 9.22 mg/L against another cyanobac- Extracts of many aquatic and terrestrial plants inhibit the terium Planktothrix rubescens (Churro et al., 2010). Even within one growth of cyanobacteria. Aquatic plants, such as Stratiotes aloides genus, the responses of different strains to one compound were (Mulderij et al., 2006), Myriophyllum spicatum (Planas et al., 1981), also different. For example the IC50 of saguainarine against Phragmites communis (Li and Hu, 2005), Ceratophyllum demersum M. aeruginosa is 0.29 mg/L (Jancula et al., 2010); however, our and Najas marina spp. Intermedia (Gross et al., 2003), reportedly laboratory results indicated that the IC50 of this compound against inhibit the growth of cyanobacteria. However, using extracts of M. aeruginosa NIES-843 was 0.035 mg/L (unpublished data). aquatic plants to control cyanobacteria seems impractical due to Another point is that there are no uniform criteria within the limitation of resources. Aquatic plants are important to mainte- published bioassays of natural chemicals against cyanobacteria. nance of a clear water regime within a water body. Excessive Many factors, such as incubating time (Chrysayi-Tokousbalides collection of aquatic plants from a water body will cause a shift of et al., 2007) and initial inoculating densities (Churro et al., regime from clear water to turbid water. The extracts of many 2009),which can also significantly influence the results, are not terrestrial plants also show inhibitory effects against cyanobacteria. well-controlled. These plants are mainly distributed among the families of Papa- The growth inhibitory effects of BDSs on algae may be either veraceae (Jancula et al., 2007), Rutaceae (Cantrell et al., 2005; algistatic or algicidal. An algistatic effect means that the target algae Purcaro et al., 2009; Meepagala et al., 2005a; Meepagala et al., may recover to growth after the removal of BDSs, whereas an 2010), Apiaceae (Meepagala et al., 2005b), Asteraceae (Ni et al., algicidal effect means that the target algae are killed and no algal 2011) and Ephedraceae (Yan et al., 2012). For instance, an extract re-growth is observed. Generally, algistatic- or algicidal-effects may of E. equisetina root exhibited good potential for controlling cya- depend on the exposed concentration. Moreover, different algae nobacteria (Yan et al., 2012). Unfortunately, due to differences in may exhibit different algistatic- or algicidal-effects to a certain level extraction processes and bioassay protocols, published accounts of BDS stress. Churro et al. (2009) reported that some eukaryotic of inhibitory efficiencies among such plant extracts are not algae exhibited algistatic effects under the stress of bacillamide at comparable. the IC50, whereas the cyanobacteria Anabaena sp. and Aphanizo- Another source of antialgal extracts are those derived from menon gracile exhibited algicidal-effects at the IC50. Those different agricultural byproducts. Gibson et al. (1990) reported that barley responses may affect the algal assemblage after the degradation of straw could inhibit the growth of many algae. Subsequently, other BDSs. Thus it is important to determine whether algistatic- or J. Shao et al. / Journal of Environmental Management 125 (2013) 149e155 151 algicidal effects, or both, are operative for a particular BDS before it of the algal cell membrane, thus causing changes in plasma mem- is adopted for algal control. However, except for a few BDSs such as brane integrity and the leakage of ions in the protoplast. Inactiva- bacillamide (Churro et al., 2009), tryptamine (Churro et al., 2010) tion of superoxide dismutase and subsequent oxidative damage to and decomposing barley straw (Newman and Barrett, 1993), we do algal cells may also be an important reason for growth inhibition of not know whether observed inhibitory effects are algistatic or Ethyl 2-methylacetoacetate on M. aeruginosa (Hong et al., 2008a, algicidal at the IC50. 2008b). However, these action mechanisms were deduced from general physiological responses of cells to interference. Specific 3. Inhibitory mechanisms of BDSs on cyanobacteria action modes, such as how ethyl 2-methylacet-oacetate changes the constituents of plasma membrane and how this compound Though many BDSs have inhibitory effects on cyanobacteria, few decreases the activities of superoxide dismutase, remain unknown. of their inhibitory mechanisms have been elucidated. Polyphenols Nonanoic acid, derived from M. spicatum (Nakai et al., 2005)is that may share a common inhibitory mechanism of oxidative a medium-chain monocarboxylic acid. Medium-chain mono- damage from polyphenol-autoxidized products (Nakai et al., 2001). carboxylic acids can affect the spatial organization of the plasma However, this explanation is based on speculation according to the membrane, and disturb functions of the membrane as a matrix for chemical characteristics of polyphenols. Direct evidence such as the enzymes and as a selective barrier, thereby leading to an increase in determination of radicals from auto-oxidation of polyphenol is the passive flow of protons through the plasma membrane and loss missed, and how the polyphenol-autoxidized products act against of plasma lemma integrity (Stevens and Hofemyer, 1993). Nonanoic cyanobacteria is still unknown now. Beside this hypothesized acid may effect this inhibitory mechanism on M. aeruginosa. explanation, other studies suggest that inhibition of alkaline However, this speculated mechanism requires research validation, phosphatase (Gross et al., 1996; Dziga et al., 2007) and interruption specifically focused on fatty acid constituents of cyanobacterial of the electron transfer chain of photosystem II (PS II) (Leu et al., plasma membranes. 2002; Dziga et al., 2007) may also be inhibitory mechanisms of Ultrastructural examination using transmission electron micro- polyphenols on Microcystis species. Interruption of the electron scopy suggests that b-ionone stress causes the distortion of the transfer via PS II often leads to the increase of deexcitation of thylakoids and the collapse of thylakoid membrane stacks. Poly- excited energy through non-photochemical pathway, which leads phasic Chlorophyll a fluorescence transient analysis indicates that to the increase of reactive oxygen species (ROS) in the cells. Shao the reaction center of PS II and the electron transport at the acceptor et al. (2009b) reported that polyphenol pyrogallic acid stress side of PS II are the targets responsible for the toxicity of b-ionone on could increase the malodialdehyde (MDA) content in the cell of M. the PS II of M. aeruginosa (Shao et al., 2011). 3-oxo-a-ionone can also aeruginosa, which confirmed that polyphenol induced oxidative damage the thylakoid membranes of cyanobacteria, interrupt the damage to the cell of M. aeruginosa since MDA is the oxidative electron transport in PS II, decrease effective quantum yields, and product of unsaturated fatty acids. Though we can confirm now, eventually lead to the failure of photosynthesis (Wu et al., 2011). that polyphenols could induce oxidative damage to cyanobacteria, Although the inhibitory mechanisms of a- and b-ionone may be we still do not know that this oxidative damage is caused by rad- similar, the reasons for the significant difference in their effective icals originated from autoxidized polyphenols or by the ROS orig- inhibitory concentrations on cyanobacteria are still unknown. inated from the cyanobacteria cell itself due interruption of the L-lysine’s inhibitory effect on M. aeruginosa has been postulated electron transfer chain of PS II, or by the cooperation of both by Takamura et al. (2004) to be due to its structural similarity to mechanisms. meso-diaminopimelic acid, allowing this amino acid to replace Oxidative damage of polyphenols originated from lignin is also meso-diaminopimelic acid in the cyanobacterial peptidoglycan regarded as the main reason for the inhibitory effects of some when L-lysine is available in relatively high concentration. How- agricultural byproducts, such as barley straw and brown-rotted ever, this explanation is not convincing. Firstly, the growth of the wood, on cyanobacteria (Pillinger et al., 1994; Ridge and Pillinger, cyanobacterium Ocillatoria sp. was not influenced by L-lysine 1996). However, those identified polyphenols alone are unlikely (Yoshichika et al., 1999) and secondly, L-histidine, another amino to sufficiently account for the antialgal action of agricultural acid that is structurally dissimilar to meso-diaminopimelic acid, byproducts. Moreover, wheat straw with high content of lignin also inhibits growth of M. aeruginosa (Yoshichika et al., 1999). Thus, shows no inhibitory effect on cyanobacteria (Ball et al., 2001). All further study is needed to explain the inhibitory mechanism of these indicate that the inhibitory mechanisms of agricultural L-lysine on cyanobacteria. byproducts on algae need further study. Alkaloids may have multiple mechanisms that act on cyano- 4. Field applications of BDSs in algal control bacteria. Previous studies indicated that sanguinarine was a phototoxic alkaloid, and that light can induce the production of Even though many antialgal BDSs have been identified, only a H2O2 and singlet molecular oxygen (Arnason et al., 1992; Görner few of them, such as L-lysine, ferulic acid, and some quinines e.g., et al., 2011). Sanguinarine also inhibits the assembly of FtsZ in 9,10-anthraquinone and its derivatives, biocide SeaKleen (quinone- Escherichia coli (Beuria et al., 2005) and induces DNA damage in based natural product), extracts of E. equisetina root and barley mouse spleen cells (Kaminskyy et al., 2008). Through the analysis of straw, have been tested for efficacy in control or removal of HABs in gene expression, Chlorophyll a fluorescence transients, and intra- field environments. L-lysine, anthraquinone-59 (2-[methylamino- cellular ROS determination, our laboratory research leads us to N-(10-methylethyl)]-9,10-anthraquinone monophosphate), biocide believe that the toxic action mechanism of sanguinarine on SeaKleen, leachates of E. equisetina root and barley straw all suc- M. aeruginosa NIES-843 may also involve DNA damage, photo- cessfully controlled target cyanobacteria in field tests, but ferulic system damage, cell division inhibition, and oxidative damage acid, 9,10-anthraquinone failed to do so (Takamura et al., 2004; (unpublished data). Oxidative damage seems also to be involved in Schrader et al., 2003, 2000, Schrader and Rimando, 2004; Schrader, the action of another alkaloid tryptamine against cyanobacteria 2007; Yan et al., 2012; Barrett et al., 1996). In field applications, since tryptamine stress could induce the lipid peroxidation and the ferulic acid failed to control musty-odor cyanobacteria in catfish formation of MDA in the cell of A. gracile (Churro et al., 2010). ponds at a spraying level of 0.97 mg/L, though the LOEC on musty- Ethyl 2-methylacetoacetate, derived from P. communis (Li and odor cyanobacterium O. cf. chalybea was as low as 0.19 mg/L. The Hu, 2005) may increase the proportions of unsaturated fatty acids rapid dissipation of this compound from pond waters may be the 152 J. Shao et al. / Journal of Environmental Management 125 (2013) 149e155 reason for its failed action (Schrader et al., 2000). Schrader et al. zooplankton, and bacteria were all increased. E. equisetina has a (1998) reported that the lowest complete inhibition concentra- long history in Traditional Chinese Medicine. It includes many tion (LCIC) for ferulic acid on O. cf. chalybea was 190 mg/L, three active secondary metabolic substances. Though the ecological orders of magnitude larger than its LOEC. Thus, we speculate that safety of this extract needs further study, Yan et al. (2012) work ferulic acid, at 0.97 mg/L, exhibits an algistatic-rather than an illuminated the great potentiality of using natural products for algicidal-effect against musty-odor cyanobacteria, and that musty- cyanobacterial control. odor cyanobacteria continue to grow after the dissipation of this compound. This may be another reason for the “failed” action of 5. Problems with using BDSs for the removal or control of ferulic acid on musty-odor cyanobacteria. Work in our laboratory cyanobacterial blooms indicated that ferulic acid had no observed adverse effect on M. aeruginosa NIES-843 at 100 mg/L (unpublished data). Differ- Though many BDSs have been screened, few are feasible can- ences between the sensitivity of assay for the musty-odor cyano- didates for application in field environments. Six principal reasons bacteria in the pond and the musty-odor cyanobacteria in the discourage application of BDSs in field environments. laboratory may also contribute the perceived failed action of this compound in the field application. (1) Some BDSs show only weak inhibitory effects on cyanobacteria. Though 9,10-anthraquinone showed the strongest inhibitory For example, b-ionone is an antialgal compound that inhibits effect on Oscillatoria perornata in laboratory tests, the application of Microcystis, but the EC50 is 22 mg/L (Shao et al., 2011). 9,10-anthraquinone failed to reduce the abundance of O. perornata (2) Cyanobacteria adapt to the inhibitory effect of some BDSs, and and cyanobacterial produced odorous levels of 2-methylisoborneol become resistant to them. Nonanoic acid was reported as in the pond. However, its water soluble derivatives successfully an allelochemical showing strong inhibitory effect on controlled the biomass of O. perornata and its production of 2- M. aeruginosa, with an EC50 as low as 0.5 mg/L (Nakai et al., methylisoborneol (Schrader et al., 2003). Results of these re- 2005); however, a following study indicated that, under the searches imply that the water solubility of an antialgal chemical is stress of nonanoic acid, cells of M. aeruginosa soon adapt to this an important consideration for possible application of natural environment (Shao et al., 2009a). antialgal chemicals. (3) Some BDSs are difficult to be obtained. Even though some natural L-lysine is one of most interesting natural antialgal compounds. antialgal chemicals strongly inhibit cyanobacteria, the supply It is a necessary amino acid for biological cells, but it shows an of these biological derived chemicals is limited, and the inhibitory effect against cyanobacteria at 0.6 mg/L (Hehmann et al., structures of those antialgal chemicals are very complex, so 2002). Thus, it may be one of the safest natural antialgal com- their chemical synthesis are difficult or prohibitively expensive. pounds. Spraying 7.3 mg/L L-lysine into a natural pond dominated For example, Tellimagrandin Ⅱ originating from M. spicatum by Microcystis resulted in a loss of Microcystis colonies within 2 shows strong inhibitory effect on Anabaena (Gross et al., 1996), days, and the dominant species shifted to Euglena spp. and/or but the content of Tellimagrandin Ⅱ in the M. spicatum is very Phormidium tenue immediately after the disappearance of Micro- low and the structure of this chemical is too complex for facile cystis (Takamura et al., 2004). The characteristics of L-lysine, such as synthesis by chemical engineers. In this way, the extract of selective toxicity to cyanobacteria, high solubility, ease of biological plants, such as barley straw, may be more applicable in algae metabolism (biodegradation), and high safety make it a promising control since it is cheaper and more easily obtained. candidate as a natural chemical in cyanobacterial control. (4) The ecological and public health risks of most BDSs are not known. Barley straw is the most recognized natural antialgal substance. Some BDSs do not specifically target cyanobacteria in aquatic Many field tests indicate that decomposing barley straw can environments; thus, using such antialgal substances may cause decrease algal biomass (Barrett et al., 1996; Everall and Lees, 1996; the collapse of aquatic ecological systems due to inhibitory or Ridge and Barrett, 1992; Barrett et al., 1999). Besides successfully lethal effects on non-target organisms. For instance, pyrogallol controlling algal biomass, enhanced invertebrate productivity strongly inhibits M. aeruginosa. However, even though the induced by barley straw also benefits fish growth. Additionally, no chemical synthesis of this allelochemical is not difficult, its adverse effect on water quality was observed during the process of putative inhibitory mechanism of oxidative damage to a wide using barley straw to control algae (Everall and Lees, 1996). How- range of biological organisms from auto-oxidation of poly- ever, in some ponds, barley straw failed to decrease algal biomass phenol may limit its application. Ethyl 2-methylacetoacetate, (Kelly and Smith, 1996; Ferrier et al., 2005). Though a wide range of another promising allelochemical for algal control, shows algae, including cyanobacteria and eukaryotic algae are susceptible strong inhibitory effects on M. aeruginosa, but it has no inhibi- to decomposing barley straw, growth of some algae were not tory effect on Chlorella vulgaris. However, selective inhibitory influenced by barley straw, and some other algae were even stim- effects are not exclusive to M. aeruginosa because ethyl 2- ulated by it. As concluded by some scientists, e.g. Martin and Ridge methylacetoacetate also strongly inhibits Chlorella pyrenoidosa (1999), Ferrier et al. (2005), the susceptibility of algae to barley (Li and Hu, 2005). Beside the potential damage of BDSs to non- straw appears not to be related to general taxonomic or structural target aquatic organisms, the health risks of BDSs to humans are features. There is no consistent, recognizable pattern that charac- also not known. As listed in the supplementary material, BDSs terizes the responses of different algae to barley straw stress. The belonging to quinones and alkaloids show strong inhibitory algal community of different water bodies differs, promoting vari- effects on cyanobacteria. Such low effective inhibition concen- able responses to barley straw; this is undoubtedly one of many trations make a presumptive case for their promise as possible reasons for the different outcomes in field applications. biologically derived chemicals for cyanobacterial control. Recently, Yan et al. (2012) described how applied extracts of E. However, previous studies suggest genotoxicity of some qui- equisetina root into ponds successfully controlled cyanobacterial- nones and alkaloids. For example, the plant-derived 1,8- blooms but did not influence nutrient concentrations in the water dihydroxyanthraquinone derivatives, emodin and danthron, column, and had no negative effect on fish survival rates and fish show genotoxicity to mouse lymphoma cells (Müeller et al., yields. The habitat conditions for macrophytes, zooplankton, and 1998). Sanguinarine was also reported to bind with DNA, and bacteria were improved after the application of E. equisetina root induce DNA damage in cells (Bai et al., 2008; Kaminskyy et al., extracts into water since the diversities of aquatic macrophytes, 2008). Genotoxic information for most BDSs listed in J. Shao et al. / Journal of Environmental Management 125 (2013) 149e155 153

supplementary material is currently unavailable. Application of easily degraded in environments in which it is used; iii) the raw BDSs antialgal agents on a broad scale in environmental waters materials for its synthesis should be ample, or its chemical synthesis may pose a health risk to aquatic animals and humans. Thus, should be facile and inexpensive; iv) it should be safe for human and genotoxicity of BDSs should be tested at the most basic level, aquatic animals. None of the currently available antialgal BDSs e.g., by the Ames Test (Ames et al.,1973) or similar means before possesses all of the above characteristics. Given the abundance of accepting their routine environmental application. evidence that BDSs have high potential as effective and environ- (5) Some BDSs may exacerbate eutrophication. BDSs such as lysine, mentally safe agents for control of cyanobacterial blooms, it is wise rice hull and wheat bran leachate include N and/or P, which may to continue isolating new BDSs with anti-cyanobacterial properties. increase bioavailable N and/or P in waters where they are Another approach to obtaining new antialgal substances is to applied, thereby exacerbating eutrophication. For example, in modify identified BDSs using chemical engineering technologies, to order to control a cyanobacteria bloom, L-lysine was sprayed better approximate ideal standards of efficacy and safety. onto the pond at a final concentration of 7.3 mg/L (Takamura et al., 2004). 7.3 mg/L lysine is equivalent to 1.4 mg/L as nitro- 6.2. Control of cyanobacterial blooms using synergistic effects of gen. The criterion of total nitrogen for eutrophication is 2 mg/L BDSs (Yang et al., 2008). So, one can speculate that frequent introduction of L-lysine into water will exacerbate eutrophication. The inhibitions of cyanobacteria by some BDSs are synergistic (6) BDS-“controlled” cyanobacterial blooms may release toxins. with those of others. For example, four polyphenols (pyrogallic Another consideration is that synthesis and release of cyano- acid, gallic acid, ellagic acid and (þ)-catechin) were identified from toxins may occur during the process of controlling cyano- cultures of the aquatic plant M. spicatum as allelochemicals bacterial blooms using BDSs. An enclosure experiment in Lake antagonistic toward cyanobacteria (Nakai et al., 2000). Zhu et al. Dianchi indicated that removal of cyanobacterial blooms using (2010) studied the combined inhibitory effects of these four poly- lysine or lysine plus malonic acid could decrease the concen- phenols against M. aeruginosa, and found apparent synergistic trations of microcystins in water column (Kaya et al., 2005), but effects. it would be optimistic to think simply that all BDSs will In an enclosure experiment in Lake Dianchi, a spray level of 10 g/ decrease cyanotoxins in water. Previous work indicates that the m2 lysine caused the cessation of cyanobacterial blooms. However, stress of some BDSs induces the up-regulation of the expres- on Day 7, Microcystis cells that had been treated with lysine started sion of genes involved in the synthesis of cyanotoxins. For growing again, and formed blooms on the 28th day, whereas in example, pyrogallol stress could induce the up-regulation of treatment sprays containing both lysine and malonic acid, no cya- the expression of mcyB, a gene in mcy gene cluster involved in nobacterial blooms were observed (Kaya et al., 2005). the synthesis of microcystins (Shao et al., 2009b). From these results, we can at least speculate that higher microcystins 6.3. Control of harmful cyanobacteria at the early stages of concentrations will result when Microcystis is under the stress proliferation of pyrogallol. Cyanotoxins, such as microcystins, mainly accu- mulate within the cells of cyanobacteria (Juttner and Luthi, As mentioned above, many bloom-forming cyanobacteria, such 2008). Stress from BDSs may lead to cell death of affected as Microcystis, Anabaena, Planktothrix, produce cyanotoxins. Stress cyanobacteria, which in turn may cause temporary increase in from BDSs may lead to the release of cyanotoxins from affected concentrations of microcystins in water due to their release cyanobacteria, which in turn may increase environmental- and from dead cyanobacterial cells. Of course, the disadvantage of public-health risk. Control of cyanobacteria before they form possible releasing of cyanotoxins is not unique to BDSs. Other blooms can reduce health risks caused by the release of cyano- approaches such as traditional chemical manipulations, phys- toxins. Therefore, in eutrophicated water bodies that typically ical manipulations are also subject to this disadvantage. One experience annual cyanobacterial blooms, the best approach may way to avoid cyanotoxins contamination is to control cyano- be to preemptively control cyanobacteria at the early stages of bacteria before they form severe blooms in water, e.g., at the proliferation. early stage of proliferation. Bloom-forming cyanobacteria have the annual life cycle of dormancy in winter, recruitment in 6.4. Evaluate ecological risks of BDSs in removal and controlling of spring, growth and floating to the water surface in summer and cyanobacterial blooms sinking to the sediment in autumn (Kong and Gao, 2005). Previous studies show that temperatures for the recruitment of As mentioned above, though many biologically originated algi- Microcystis and Anabaena were 15 C and 18 C(Karlsson and cides have been isolated and their inhibitory effects on cyanobac- Brunberg, 2004; Li et al., 2004), respectively. However, infor- teria have been tested, information on their toxicology relative to mation about the efficacy of BDSs against cyanobacteria under other aquatic organisms and humans is very limited. Thus, such temperatures is unavailable. Thus, elucidation of re- ecological- and public health- risks of most antialgal BDSs in algae sponses of cyanobacteria to BDSs under low temperatures is removal should be carefully evaluated in the context of the dearth critically important for development of effective BDS control of of ecological- and public-health risk studies. To mitigate this harmful cyanobacteria at the early stages of proliferation. knowledge gap, studies should not be focused on inhibitory effects of BDSs on cyanobacteria, but rather on their possible toxic effects on non-target aquatic organisms, general ecotoxicological impacts 6. Guidelines for application of BDSs for control of and even on toxicity toward humans. cyanobacteria in aquatic ecosystems Many organisms, including bacteria, cyanobacteria, eukaryotic algae, zooplankton, invertebrates, aquatic plants, and fishes co- 6.1. Screening of new BDSs exist in water ecosystems. The ecological risk evaluation for BDSs in cyanobacterial control in natural water bodies should at least A good BDS for control of cyanobacterial blooms should have at include the following elements: i) determine the changes of target least the following characteristics: i) it should show strong selective cyanobacterial biomass; ii) monitor biomass and diversity of non- inhibitory effect on bloom-forming cyanobacteria; ii) it should be target groups; iii) determine the dynamics of BDSs in any treated 154 J. Shao et al. / Journal of Environmental Management 125 (2013) 149e155 water body; iv) assess and characterize cyanotoxins in water Gross, E.M., Erhard, D., Iványi, E., 2003. Allelopathic activity of Ceratophyllum bodies, and; v) evaluate genetic toxicity and carcinogenic potential demersum L. and Najas marina ssp. intermedia (Wolfgang) Casper. Hydrobiologia 506e509, 583e589. of any applied BDSs. Hehmann, A., Kaya, K., Watanabe, M.M., 2002. Selective control of Microcystis using With such sound bases, a more realistic evaluation of the an amino acid e a laboratory assay. J. Appl. Phycol. 14, 85e89. ecological risk of these antialgal BDSs for control of water blooms of Hong, Y., Hu, H.Y., Xie, X., Li, F.M., 2008a. Responses of enzymatic antioxidants and non-enzymatic antioxidants in the cyanobacterium Microcystis aeruginosa to cyanobacteria is possible. Only ecologically secure and well-vetted the allelochemical ethyl 2-methyl acetoacetate (EMA) isolated from reed broad applications of BDSs for cyanobacteria control should be (Phragmites communis). J. Plant Physiol. 165, 1264e1273. considered as feasible. Hong, Y., Hu, H.Y., Xie, X., Li, F.M., 2008b. Physiological and biochemical effects of allelochemical ethyl 2-methyl acetoacetate (EMA) on cyanobacterium Micro- cystis aeruginosa. Ecotoxicol. Environmen. Saf. 71, 527e534. Jancula, D., Gregorova, J., Marsálek, B., 2010. Algicidal and cyanocidal effects of Acknowledgements selected isoquinoline alkaloids. Aquac. Res. 41, 598e601. Jancula, D., Marsálek, B., 2011. Critical review of actually available chemical com- The work was supported by the National Natural Science pounds for prevention and management of cyanobacterial blooms. Chemo- e Foundation of China (No. 21107024), Hunan Provincial Key Labo- sphere 85, 1415 1422. Jancula, D., Suchomelová, J., Gregor, J., Smutná, M., Marsálek, B., Táborská, E., 2007. ratory of Farmland Pollution Control and Agricultural Resources Effects of aqueous extracts from five species of the family Papaveraceae on Use, and the Foundation of Furong Scholar Project of Hunan Prov- selected aquatic organisms. Environ. Toxicol. 22, 480e486. ince, and an honorary professorship (J-D Gu). Juttner, F., Luthi, H., 2008. Topology and enhanced toxicity of bound microcystins in Microcystis PCC 7806. Toxicon 51, 388e397. Kaminskyy, V., Lin, K.W., Filyak, Y., Stoika, R., 2008. Differential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary Appendix A. Supplementary Material mouse spleen cells and mouse leukemic cells. Cell. Biol. Int. 32, 271e277. Karlsson, E.I., Brunberg, A.K., 2004. The importance of shallow sediments in the Supplementary data related to this article can be found online at recruitment of Anabaena and Aphanizomenon (cyanophyceae). J. Phycol. 40, 831e836. http://dx.doi.org/10.1016/j.jenvman.2013.04.001. Kaya, K., Liu, Y.D., Shen, Y.W., Xiao, B.D., Sano, T., 2005. Selective control of toxic Microcystis water blooms using lysine and malonic acid: an enclosure experiment. Environmen. Toxicol. 20, 170e178. References Kaya, K., Sano, T., 1996. Algicidal compounds in yeast extract as a component of microbial culture media. Phycologia 35, 117e119. Ames, B.N., Durston, W.E., Yamaski, E., Lee, F.D., 1973. Carcinogens are mutagens: a Kelly, L.A., Smith, S., 1996. The nutrient budget of a small eutrophic loch and the simple test system combining liver homogenates for activation and bacteria for effectiveness of straw bales in controlling algal blooms. Freshwater Biol. 36, detection. Proc. Natl. Acad. Sci. 70, 2281e2285. 411e418. Anderson, D.M., 1997. Turning back the harmful red tides. Nature 38, 513e514. Kong, F.X., Gao, G., 2005. Hypothesis on cyanobacteria bloom-forming mechanism Arnason, J.T., Guèrin, B., Kraml, M.M., Mehta, B., Redmond, R.W., Scaiano, J.C., 1992. in large shallow eutrophic lakes. Acta Ecol. Sinica 25, 589e595. Phototoxic and photochemical properties of sanguinarine. Photochem. Photo- Leu, E., Krieger-Liszkay, A., Goussias, C., Gross, E.M., 2002. Polyphenolic alle- biol. 55, 35e38. lochemicals from the aquatic angiosperm Myriophyllum spicatum inhibit Bai, L.P., Cai, Z., Zhao, Z.Z., Nakatani, K., Jiang, Z.H., 2008. Site-specific binding of photosystem II. Plant Physiol. 130, 2011e2018. chelerythrine and sanguinarine to single pyrimidine bulges in hairpin DNA. Li, F.M., Hu, H.Y., 2005. Isolation and characterization of a novel antialgal Anal. Bioanal. Chem. 392, 709e716. allelochemical fromPhragmitescommunis. Appl. Environ. Microbiol. 71,6545e6553. Ball, A.S., Williams, M., Vincent, D., Robinson, J., 2001. Algal growth control by a Li, K.Y., Song, L.R., Wan, N., 2004. Studies on recruitment and growth characteristic barley straw extract. Bioresour. Technol. 77, 177e181. of Microcystis in sediment. Acta Hydrobiol. Sinica 28, 113e118. Barrett, P.R.F., Littlejohn, J.W., Curnow, J., 1999. Long-term algal control in a reservoir Liang, Y.B., Bi, Y.H., Liu, G.X., Hu, Z.Y., 2010. Effect of extract from three citrus peels using barley straw. Hydrobiologia 415, 309e313. on growth of Microcystis aeruginosa PCC7806. J. Wuhan Botan. Res. 28, 43e48. Barrett, P.R.F., Curnow, J.C., Littlejohn, J.W., 1996. The control of diatom and cyano- (Chinese Journal). bacterial blooms in reservoirs using barley straw. Hydrobiologia 340, 307e311. Lopez, C.B., Jewett, E.B., Dortch, Q., Walton, B.T., Hudnell, H.K., 2008. Scientific Beuria, T.K., Santra, M.K., Panda, D., 2005. Sanguinarine blocks cytokinesis in bac- assessment of freshwater harmful algal blooms. In: Interagency Working Group teria by inhibiting FtsZ assembly and bundling. Biochemistry 44, 16584e16593. on Harmful Algal Blooms, Hypoxia, and Human Health of the Joint Subcom- Cantrell, C.L., Schrader, K.K., Mamonov, L.K., Sitpaeva, G.T., Kustova, T.S., Dunbar, C., mittee on Ocean Science and Technology. Washington, DC. Wedge, D.E., 2005. Isolation and identification of antifungal and antialgal al- Martin, D., Ridge, I., 1999. The relative sensitivity of algae to decomposing barley kaloids from Haplophyllum sieversii. J. Agric. Food Chem. 53, 7741e7748. straw. J. Appl. Phycol. 11, 285e291. Chrysayi-Tokousbalides, M., Machera, K., Kyriakopoulou, K., Aliferis, K.A., Meepagala, K.M., Schrader, K.K., Burandt, C.L., Wedge, D.E., Duke, S.O., 2010. New Schrader, K.K., Tsoutsanis, I., Anastasiadou, P., 2007. Comparative toxicity of the class of algicidal compounds and fungicidal activities derived from a chromene phytotoxins (8R,16R)-(-)-pyrenophorin and (5S,8R,13S,16R)-(-)-pyrenophorol amide of Amyris texana. J. Agric. Food Chem. 58, 9476e9482. on aquatic organisms. Bull. Environ. Contam. Toxicol. 79, 499e503. Meepagala, K.M., Schrader, K.K., Wedge, D.E., Duke, S.O., 2005a. Algicidal and Churro, C., Alverca, E., Sam-Bento, F., Paulino, S., Figueira, V.C., Bento, A.J., antifungal compounds from the roots of Ruta graveolens and synthesis of their Prabhakar, S., Lobo, A.M., Calado, A.J., Pereira, P., 2009. Effects of bacillamide and analogs. Phytochemistry 66, 2689e2695. newly synthesized derivatives on the growth of cyanobacteria and microalgae Meepagala, K.M., Sturtz, G., Wedge, D.E., Schrader, K.K., Duke, S.O., 2005b. Phyto- cultures. J. Appl. Phycol. 21, 429e442. toxic and antifungal compounds from two Apiaceae species, Lomatium cal- Churro, C., Fernandes, A.S., Alverca, E., Sam-Bento, F., Paulino, S., Figueira, V.C., ifornicum and Ligusticum hultenii, rich sources of Z-ligustilide and apiol, Bento, A.J., Prabhakar, S., Lobo, A.M., Martins, L.L., Mourato, M.P., Pereira, P., respectively. J. Chem. Ecol. 31, 1567e1578. 2010. Effects of tryptamine on growth, ultrastructure and oxidative stress of Müeller, S.O., Lutz, W.K., Stopper, H., 1998. Factors affecting the genotoxic potency cyanobacteria and microalgae cultures. Hydrobiologia 649, 195e206. ranking of natural anthraquinones in mammalian cell culture systems. Mutat. Dziga, D., Suda, M., Bialczyk, J., Urszula, C.P., Lechowski, Z., 2007. The alteration of Res. 414, 125e129. Microcystis aeruginosa biomass and dissolved microcystin-LR concentration Mulderij, G., Smolders Alfons, J.P., van Donk, E., 2006. Allelopathic effect of the following exposure to plant-producing phenols. Environ. Toxicol. 22, 341e346. aquatic macrophyte, Stratiotes aloides, on natural phytoplankton. Freshwater Everall, N.C., Lees, D.R., 1996. The use of barley-straw to control general and blue- Biol. 51, 554e561. green algal. Wat. Res. 30, 269e276. Nakai, S., Inoue, Y., Hosomi, M., 2001. Algal growth inhibition effects and induce- Ferrier, M.D., Butler Sr, B.R., Terlizzi, D.E., Lacouture, R.V., 2005. The effects of barley ment modes by plant-producing phenols. Water Res. 35, 1855e1859. straw (Hordeum vulgare) on the growth of freshwater algae. Bioresour. Technol. Nakai, S., Yamada, S., Hosomi, M., 2005. Anti-cyanobacterial fatty acids released 96, 1788e1795. from Myriophyllum spicatum. Hydrobiologia 543, 71e78. Gao, L., Xie, L., 2011. Analysis of the influence of meteorological condition on cya- Nakai, S., Inoue, Y., Hosomi, M., Murakami, A., 2000. Myriophyllum spicatum nobacterial bloom and treatment methods in Taihu Lake. China Resour. Compr. released allelopathic polyphenols inhibiting growth of blue-green algae Utilization 29, 35e38. Microcystis aeruginosa. Water Res. 34, 3026e3032. Gibson, M.T., Welch, I.M., Barrett, P.R.F., Ridge, I., 1990. Barley straw as an inhibitor of Newman, J.R., Barrett, P.R.F., 1993. Control of Microcystis aeruginosa by decomposing algal growth II: laboratory studies. J. Appl. Phycol. 2, 241e248. barley straw. J. Aquat. Plant Manage. 31, 203e206. Görner, H., Miskolczy, Z., Megyesi, M., Biczók, L., 2011. Photooxidation of alkaloids: Ni, L., Chen, S., Ren, G., Hao, X., 2011. Advance research on the allelopathy of considerable quantum yield enhancement by rose bengal-sensitized singlet terrestrial plants in inhibition of algae. Ecol. Environ. Sic 20, 1176e1182. (Chi- molecular oxygen generation. Photochem. Photobiol. 87, 1315e1320. nese journal). Gross, E.M., Meyer, H., Schilling, G., 1996. Release and ecological impact of algi- Park, M.H., Chung, I.M., Ahmad, A., Kim, B.H., Hwang, S.J., 2009. Growth inhibition of cidal hydrolysable polyphenols in Myriophyllum spicatum. Phytochemistry 41, unicellular and colonial Microcystis strains (Cyanophyceae) by compounds 133e138. isolated from rice (Oryza sativa) hulls. Aquat. Bot. 90, 309e314. J. Shao et al. / Journal of Environmental Management 125 (2013) 149e155 155

Park, M.H., Han, M.S., Ahn, C.Y., Kim, H.S., Yoon, B.D., Oh, H.M., 2006. Growth in- algicides against the musty-odor cyanobacterium Oscillatoria perornata. Appl. hibition of bloom-forming cyanobacterium Microcystis aeruginosa by rice straw Environ. Microbiol. 69, 5319e5327. extract. Lett. Appl. Microbiol. 43, 307e312. Shao, J., Wu, X., Li, R., 2009a. Physiological responses of Microcystis aeruginosa Pillinger, J.M., Cooper, J.A., Ridge, I., 1994. Role of phenolic compounds in the PCC7806 to nonanoic acid stress. Environmen. Toxicol. 24, 610e617. antialgal activity of barley straw. J. Chem. Ecol. 20, 1557e1569. Shao, J., Wu, Z., Yu, G., Peng, X., Li, R., 2009b. Allelopathic mechanism of pyrogallol Pillinger, J.M., Gilmour, I., Ridge, I., 1995. Comparison of the antialgal acitivity of to Microcystis aeruginosa PCC7806 (Cyanobacteria): from views of gene brown-rotted and white-rotted wood and in situ analysis of lignin. J. Chem. Ecol. expression and antioxidant system. Chemosphere 75, 924e928. 21, 1113e1125. Shao, J., Xu, Y., Wang, Z., Jiang, Y., Yu, G., Peng, X., Li, R., 2011. Elucidating the toxicity Planas, D., Sarhan, F., Dube, L., Godmaire, H., Cadieux, C., 1981. Ecological signifi- targets of b-ionone on photosynthetic system of Microcystis aeruginosa NIES- cance of phenolic compounds of Myriophyllum spicatum. Verh. Internat. Verein. 843 (Cyanobacteria). Aquatic. Toxicol. 104, 48e55. Limnol 21, 1492e1496. Shao, J., Yu, G., Wang, Z., Wu, Z., Peng, X., Li, R., 2010. Towards clarification of the Purcaro, R., Schrader, K.K., Burandt, C., DellaGreca, M., Meepagala, K.M., 2009. inhibitory mechanism of wheat bran leachate on Microcystis aeruginosa NIES- Algicide constituents from Swinglea glutinosa. J. Agric. Food Chem. 57, 843 (cyanobacteria): physiological responses. Ecotoxicology 19, 1634e1641. 10632e10635. Stevens, S., Hofemyer, J.H.S., 1993. Effects of ethanol, octanoic and decanoic acids on Ridge, I., Barrett, P.R.F., 1992. Algal control with barley straw. Aspects Appl. Biol. 29, fermentation and the passive influx of protons through the plasma membrane 457e462. of Saccharomyces cerevisiae. Appl. Microbiol. Biotech. 38, 656e663. Ridge, I., Pillinger, I.M., 1996. Towards understanding the nature of algal inhibitors Takamura, Y., Yamada, T., Kimoto, A., Kanehama, N., Tanaka, T., Nakadaira, S., Yagi, O., from barley straw. Hydrobiologia 340, 301e305. 2004. Growth inhibition of Microcystis cyanobacteria by L-Lysine and disappear- Ridge, I., Pillinger, J.M., Walters, J., 1995. Alleviating the problems of excessive algal ance of natural Microcystis blooms with spraying. Microbe. Environ. 19, 31e39. growth. In: Harper, D.M., Ferguson, A.J.D. (Eds.), The Ecological Basis for River Visser, P.M., Ibelings, B.W., Mur, L.R., Walsby, A.E., 2005. The ecophysiology of the Management. John Wiley, New York, pp. 211e218. harmful cyanobacterium Microcystis: features explaining its success and Schrader, K.K., Rimando, A., 2004. Evaluation of the natural product SeaKleen for measures for its control. In: Matthijs, J., Hans, C.P., Visser, P.M. (Eds.), Harmful controlling the musty-odor-producing cyanobacterium Oscillatoria perornata in Cyanobacteria. Huisman, Springer, AH Dordrecht, Netherlands, pp. 109e142. catfish ponds. N. Am. J. Aquacult. 66, 20e28. Wu, Y., Liu, J., Yang, L., Chen, H., Zhang, S., Zhao, H., Zhang, N., 2011. Allelopathic Schrader, K.K., 2007. Preliminary pond evaluation of a natural-based algicide for control of cyanobacterial blooms by periphyton biofilms. Environmen. Micro- managing musty off-flavor in channel catfish aquaculture. N. Am. J. Aquacult. biol. 13, 604e615. 69, 360e366. Yan, R., Ji, H., Wu, Y., Kerr, P.G., Fang, Y., Yang, L., 2012. An investigation into the Schrader, K.K., de Regt, M.Q., Tidwell, P.R., Tucker, C.S., Duke, S.O., 1998. Se- kinetics and mechanism of the removal of cyanobacteria by extract of Ephedra lective growth inhibition of the musty-odor producing cyanobacterium equisetina root. PLoS One 7, e42285. Oscillatoria cf. chalybea by natural compounds. Bull. Environ. Contam. Yang, X.E., Wu, X., Hao, H.L., He, Z.L., 2008. Mechanisms and assessment of water Toxicol. 60, 651e658. eutrophication. J. Zhejiang Univ. Sci. B 9, 197e209. Schrader, K.K., Duke, S.O., Kingsbury, S.K., Tucker, C.S., Duke, M.V., Dionigi, C.P., Yoshichika, T., Mariko, C., Ayako, O., Hirofumi, N., Osami, Y., 1999. Growth responses Millie, D.F., Zimba, P.V., 2000. Evaluation of ferulic acid for controlling the of Microcystis and Oscillatoria cyanobacteria to various organic compounds and musty-odor cyanobacterium, Oscillatoria perornata, in aquaculture ponds. growth inhibition by L-Lysine and L-Histidine. Environ. Sci. 12, 329e337. J. Appl. Aquacult. 10 (1), 1e16. Zhu, J., Liu, B., Wang, J., Gao, Y., Wu, Z., 2010. Study on the mechanism of allelopathic Schrader, K.K., Nanayakkara, N.P.D., Tucker, C.S., Rimando, A.M., Ganzera, M., influence on cyanobacteria and chlorophytes by submerged macrophyte Schaneberg, B.T., 2003. Novel derivatives of 9,10-anthraquinone are selective (Myriophyllum spicatum) and its secretion. Aquatic. Toxicol. 98, 196e203.