Pharmaceutical Communication Biosci. Biotech. Res. Comm. 11(3): 356-362 (2018) Clinical uses and toxicity of Ergot, Claviceps purpurea An evidence-based comprehensive retrospective review (2003-2017) Raghad Al-Omari1, Atheer Al-Enazi1, Rizwan Ahmad*2, Niyaz Ahmad3, Atta Abbas Naqvi4 and Adeeb Shehzad5 1College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 2Natural Products and Alternative Medicines, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 3Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 4Department of Pharmacy Practice, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 5Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan ABSTRACT Ergot alkaloids produced by the fungus Claviceps parasitizing on cereals presents a high toxicity risk for animals and humans due to presence of its alkaloid content. Ergot-alkaloid toxicity occurs via their medicinal use however human poisoning from ergot plant is rare. The aim of this review is to determine the toxicity of ergot plant or ergot- amine derivatives in humans. Databases such as Google scholar, PubMed, Scopus, Web of Science alongwith related books and theses as well as the library resources from Imam Abdulrahman Bin Faisal University were used whereas the Key words searched included; Ergot, Egotism, Ergotamine poisoning, Ergotamine interaction with HIV therapy, Ergotamine overdose, and report cases of ergotism. The relevant literature search suggests many toxicity cases and side effects associated with the use of ergot-alkaloids. More commonly it develops a condition known as ergotism i.e. a disease or toxic condition produced by eating ergot grains or rye or chronic use of ergot drug. The characteristic ARTICLE INFORMATION: *Corresponding Author: [email protected] Received 1st July, 2018 Accepted after revision 21st Sep, 2018 BBRC Print ISSN: 0974-6455 Online ISSN: 2321-4007 CODEN: USA BBRCBA Thomson Reuters ISI ESC / Clarivate Analytics USA and Crossref Indexed Journal NAAS Journal Score 2018: 4.31 SJIF 2017: 4.196 © A Society of Science and Nature Publication, Bhopal India 2018. All rights reserved. Online Contents Available at: http//www.bbrc.in/ DOI: 10.21786/bbrc/11.3/2 356 Raghad Al-Omari et al. features of ergotism consist of painful and cold extremities. Furthermore, a notable and severe interaction of ergot- alkaloids was found in HIV patients using ergotamine and antiretroviral drugs together. Ergotamine which is one of ergot preparation has poisonous effect when taken in over dose and it interacts with antiretroviral drugs also. KEY WORDS: EGOTISM; MIGRAINE HEADACHE; POSTPARTUM HEMORRHAGE; ARTERIAL SPASM; CYANOSIS INTRODUCTION In addition, ergot induces cytotoxic and apoptotic effect shows anti-cancer effect and thus used as a can- The ergot fungus (Claviceps purpurea) is family of sec- cer therapy. In a study on two cancer lines (Hep-G2 ondary metabolites and is a common seed pathogen and HT-29) ergot showed a high grade apoptotic effect, of grasses and cereals. Ergot is a parasitic fungus that (Mulac et al., 2013). Furthermore, ergot alkaloids have belongs to the genus Claviceps and forms dark sclerotia an important widespread use in migraine headaches and on various grasses and grains. After maturing, the scle- 5-hydroxytryptamine (5-HT) receptors acts as binding site rotia fall to the ground and remain partially buried for for these ergot derivatives such as Ergotamine, Dihydro- the resting stage of ergot formation. This period occurs ergotamine, and Methysergide. They work as agonist of during cold or winter weather, (Ehrlich et al., 2013). 5-HT1B, 5-HT1D, and 5-HT1F receptors to treat for treat- Ergot plant has medicinal uses to treat some diseases; ment as well as prophylaxis for migraine headache with a even though, Ergot contain alkaloids which can cause high effi cacy, (Dholf et al., 2012). Though in human, ergot severe toxicity in mammals when ingested and thus the complications i.e. ergotism appears rarely with symptoms fungal infection might provide protection for the host such as tachycardia, hypertension and arterial spasm, still plant against mammalian herbivores, (Panaccione et al., it is important to be taken care as ergot acts as a strong 2012). Ergot alkaloids are natural products having nitro- vasoconstrictor and may cause severe adverse effects at gen indole alkaloids. There are three group of ergot; I. cardiac and limbs level, (Adam et al., 2014). peptides (ergopeptines), II. Clavines and III. Lysergic acid Current review aims to highlight the more impor- amides, (Gerhards et al., 2014). tant and recently reported cases regarding ergotism in There are more than fourty known ergot and usu- humans with major symptoms observed, as associated ally six of them may cause toxicity by interaction with with the use of ergot-alkaloids. The literature will be neurotransmitters. These are ergotamine, ergocornine, searched to extract out the factors behind ergotism and ergocryptine, ergocristine, ergosine and ergometrine, to report the possible measure in order to tackle such (Mulac et al., 2011). Ergot alkaloids have pharmacological reasons. The study owes importance as it will compare and toxicological effect on several receptor systems in the the therapeutic and toxic profi le for ergot and to con- human body. Ergot become activated in the body to some clude an overall scenario of how to use ergot-alkaloids receptors and show cytotoxic affects and induces apopto- for therapeutic purposes and to avoid ergotism. sis in human primary cells, (Mulac et al., 2013). Ergotism occurs when either the fungus is ingested via the contamination of grain, for example, rye or by MATERIAL AND METHODS the medicinal use of drugs derived from ergotamine compounds. Ergot toxicity called Ergotism previously Various databases searched were: Google scholar, Sci- known as Holy Fire, in some cases may lead to death, ence direct, Research gate, Web of Science, PubMed, (Floss, 1976). There are two forms of Ergotism; gangre- Science Finder, Scopus and Journals such as; Journal nous and convulsive and both can occur in the same of Ethnopharmacology, Frontier in Ethnopharmacology, individual. Gangrenous named as Saint Anthony’s, usu- Thieme journals, Clinical Toxicology journal, Journal of ally characterized by pain in one limb particularly the Agricultural and Food Chemistry, Journals of Toxicol- calf and leg, infl amed, swollen, and violet hand and foot ogy, Canadian Medical Association Journal, JSM foot whereas in severe cases the limb will separate from the and ankle journal, Toxicology and Industrial Health knee with hemorrhage and may need a knee amputa- (SAGE journals) and The Royal College of Physician of tion. The other form of ergotism i.e. convulsive form Edinburgh were searched. In addition, books and the- is accompanied with heaviness and numbness in limbs ses and online as well as hard resources from library of with paresthesia well as diarrhea without vomiting. In Imam Abdulrahman Bin Faisal University Damam, Saudi humans, ergot is used pharmacologically to inhibit lac- Arabia was also searched. tation, postpartum hemorrhage, and induce labor, (Lee Key words were also searched: and Coll, 2009). Previously ergot was used in the treat- ment of Parkinsonism and other endocrine and neuro- Ergot, Ergot alkaloids, reported case of Ergot toxicity, logical disorders, (Tesh, 2015). adverse effects of ergot; ergotism, ergotamine toxicity, BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS A COMPREHENSIVE REVIEW OF ERGOT 357 Raghad Al-Omari et al. clinical cases observed for ergot alkaloids, uses of ergot instead of naloxone for respiratory depression. Soon alkaloids, interactions of ergot alkaloids. after administration he suffered from capillary refi ll, The literature was searched for retrospective fi fteen low oxygen saturation, his hand and feet became warm years i.e. 2003-2017. All the clinical cases regarding ergot and pink and after sometime his color became grey with toxicity or ergotism were gathered and fi ltered as per the development of hypercarbia (partial pressure of carbon inclusion and exclusion criteria as mentioned below; dioxide). The infant was put on mechanical ventilation and treated with nitroprusside infusion. The condition Inclusion criteria recovered with 10 days of hospital treatment, (Bangh The clinical cases reported in humans associated with et al., 2005). the use of ergot or ergot alkaloids in any of its form C. Clinical case reported in 2009 used, were included. The toxicity resulted due to over- dose, long term use as well as any adverse effect and iii. Ergotamine with caffeine drug interaction of ergot and ergot derivatives with HIV A 28-year old patient reported to hospital with pain in drugs were also included in the study. both legs. Upon history it was revealed that the patient Exclusion criteria used ergotamine tartrate (1 mg) with caffeine (100 mg) for 3 days, due to a bi temporal headache a week ago. Clinical cases regarding ergot toxicity, reported in ani- Thus he developed the symptoms of severe leg pains, mals or in vivo studies (cell lines) as well as in vitro stud- especially below the ankle with cold and purple legs. ies were excluded from the study. Any clinical report with Hands were also cold but without any pain.