Nanomed. J. 5(1): 52-56, Winter 2018 RESEARCH PAPER The protective effect of selenium nanoparticles and selenium against paracetamol Neda Fakhr Mobasheri 1, Kahin Shahanipour 1*, Ramesh Monajemi 2 1Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran 2Department of Biology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran ABSTRACT Objective(s): Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets.The objective of this study was to determine the protective ability of selenium nanoparticles compared to selenium against parasetamol hepatotoxicity and GPX concentration. Materials and Methods: Seventy-two male rats were used in the study, and arbitrarily assigned to six groups. There were 12 rats in each group that six rat were tested in each period. Blood samples were collected from rats for measuring liver enzymes and GPX activity. Results: The present study shows that parasetamol has a toxic effect on the liver as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant increases in ALP, AST, ALT and LDH activity which was accom panied by significant decrease in GPX activity in the parasetamol -treated group compared to the control, selenium and selenium nanoparticles groups. There was no significant difference between selenium and selenium nanoparticles groups and two period time (15 and 30 day). Conclusion: selenium nanoparticles and selenium have protective against paracetamol. Keywords: GPX activity,Hepatotoxicity, Parasetamol, Selenium nanoparticles How to cite this article Fakhr mobasheri N, Shahanipour K, Monajemi R. The protective effect of selenium nanoparticles and selenium against paracetamol. Nanomed J. 2018; 5(1): 52-56. DOI: 10.22038/nmj.2018.05.008 INTRODUCTION Selenium was shown to reduce heavy metal Asetaminophen, the most widely used toxicities many years ago [10]. The administration analgesic in the world, causes severe hepatic of selenium has proved to be highly effective necrosis leading to acute liver failure (ALF) in preventing the toxicity to cadmium [11] and after suicidal overdoses [1-3]. Unintentional various mercuric compounds [12]. Selenium was liver injury from self-medication for pain or shown to protect against the hepatotoxic effect fever that leads to daily doses exceeding the of certain substances causing hepatic necrosis; 4 g/day package recommendations is also e.g., carbon tetrachloride [13] and bromobenzene well-recognized [4-7]. Work from Dr. Gillette’s [14]. The protective effects of selenium have been laboratory firmly established the importance of attributed to enhanced activity of glutathione metabolism in acetaminophen toxicity. It was peroxidase, which brings about the destruction of shown that acetaminophen is metabolically excess lipid peroxides by reducing them to hydroxy activated by cytochrome P450 to form a reactive acids. In this connection, it is of interest to note metabolite that covalently binds to protein; the that Eaton et aL (1980) [15] and Chung and Maines reactive metabolite was found to be N-acetyl-p- (1981) [16] have observed increased glutathione benzoquinone imine (NAPQI1), which is formed by levels in livers of rats after single doses of selenite, a direct two-electron oxidation [8-9]. suggesting the importance of this metabolic effect * Corresponding Author Email: [email protected] for detoxification reactions. Studies by Schnell Note. This manuscript was submitted on October 25, 2017; et al. (1983) [17] have shown that selenium approved on December 15, 2017 pretreatment can also inhibit in a dose-dependent This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. N. Fakhr Mobasheri et al. / Selenium nanoparticles and selenium against paracetamol manner the cytochrome P-450-dependent enzyme These selenium nanoparticles also show high system in male rats. Following the administration biological activity and good absorptive ability of selenite (30µmol Se/kg) cytochrome P-450 levels due to the interaction between the nanoparticles and ethylmorphine N-demethylase activity were and −NH2, C=O, −COO, and −C−N− groups of significantly decreased in male rats. Additional proteins [20]. Studies on the biological activities of studies also showed that same pretreatment to selenium and its nanoforms revealed that hollow prolong the hypnosis of pentobarbital [17]. spherical nanoparticles of selenium have strong Recently, the introduction of nanosize antioxidant properties [21]. elemental selenium produced a highly effective Similar studies declared that nano-selenium molecular compound, and when compared with has the ability to act as an antioxidant with SeMet, it showed similar efficacy in increasing reduced risk of ordinary selenium toxicity [22]. antioxidant GPx activity while displaying lower The size of nano-selenium plays an important toxicity [18]. Nano-selenium has potent effects role in its biological activity, as 5–200 nm nano on upregulation of GPx, and it yields more Se can directly scavenge free radicals in vitro in efficacious results in the induction of glutathione a size-dependent fashion [19]. The objectives of S-transferase over the short term, but it causes this investigation were to examine the ability of less oxidative stress [19]. selenium and selenium nanoparticles to prevent 120 ** 100 ** 80 60 40 MEAN OF ALT ALT OF ACTIVITY MEAN (IU/L) 20 0 selenium + selenium Np control paracetamol selenium selenium Np paracetamol +paracetamol 15day 51.57 88 54.57 61.14 60.78 68.28 30 day 52 98 57 63 64 70 Fig 1. Average activity of an Alanine aminotransferase (ALT IU/L) in different groups. ** Indicating a significant difference (P-value<0.001) between the two time periods 250 ** 200 ** 150 100 Mean of AST (IU/L) activity (IU/L) AST of Mean 50 0 selenium + selenium Np control paracetamol selenium selenium Np paracetamol +paracetamol 15day 116.57 186.86 134.14 138 144.43 152 30 day 118 208 133 140 146 156 Fig 2. Average activity of an Aspartate amino transferase (AST IU/L) in different groups. ** Indicating a significant difference (P-value<0.001) between the two time periods Nanomed. J. 5(1): 52-56, Winter 2018 53 N. Fakhr mobasheri et al. / selenium nanoparticles and selenium against paracetamol the acetaminophen-induced hepatotoxicity and Animal treatment activity of antioxidant enzyme system to explore Seventy-two male rats were used in the study, possible mechanisms by which selenium and and arbitrarily assigned to 6 groups. Group 1 was selenium nanoparticles can produce its protective the control group, and was given phosphate- action. buffered saline. Group 2 was the Selenium-treated groups and was given 1mg/Kg Na2SeO3 weight MATERIALS AND METHODS intraperitoneally as a single dose for 15 and 30 Animals days. Group 3 was the nano-selenium-treated Young (n = 12, age 3 months) and middle aged (Iranian Nanomaterials Pioneers Co.) groups and (n = 12, age 18 months) Wistar male rats were was given selenium nanoparticles (size 10–40 nm) housed in a thermoneutral environment (22 ± 2 0.5 mg/kg body weight intraperitoneally daily for 0C), on a 12: 12h photoperiod, and were provided 15 and 30 days. Group 4 was the Selenium-treated food and water as needed. This investigation groups, which received selenium 1 mg/kg for 15 was carried out in accordance with the Guide and 30 days and a single dose of paracetamol 40 for the Care and Use of Laboratory published by mg/Kg on the 5 day. Group 5 was the Selenium- the US National Institute of Health and approved treated groups, which received selenium by the institutional animal care committee (NIH nanoparticles (size 10–40 nm) for 15 and 30 days publication number 85-23, revised 1996). and a single dose of paracetamol 40 mg/Kg on 900 800 ** ** 700 600 500 * * 400 ALP (IU/L) ALP 300 200 100 0 selenium + selenium Np control paracetamol selenium selenium Np paracetamol +paracetamol 15day 562.65 732.14 442.57 516.43 479.43 511 30 day 565 745 446 523 485 518 Fig 3. Average activity of an Alkaline phosphatase (ALP IU/L) in different groups. ** Indicating a significant difference (P-value<0.001) between the two time periods. * Indicating a significant difference (P-value<0.05) between the two time periods 3000 2500 ** ** 2000 1500 1000 Mean of LDHof Mean activity (IU/L) 500 0 selenium Np selenium + control paracetamol selenium selenium Np +paracetam paracetamol ol 15day 1748.29 2390.7 1537.14 1556.14 1809.57 1800.14 30 day 1749 2425 1580 1590 1987 1869 Fig 4. Average activity of a Lactate dehydrogenase (LDH or LD IU/L) in different groups. ** Indicating a significant difference (P-value<0.001) between the two time periods. * Indicating a significant difference (P-value<0.05) between the two time periods 54 Nanomed. J. 5(1): 52-56, Winter 2018 N. Fakhr Mobasheri et al. / Selenium nanoparticles and selenium against paracetamol 450 400 350 300 250 200 ** ** 150 100 Mean of GPX (IU/L) activity 50 0 selenium Np selenium + control paracetamol selenium selenium Np +paracetam paracetamol ol 15day 250 160 350 310 320 300 30 day 256 150 360 320 324 319 Fig 5. Average activity of a Glutathione peroxidase (GPX IU/L) in different groups. ** Indicating a significant difference (P-value<0.001) between the two time periods the 5 day. Group 6 was the paracetamol-treated 4 (nano-selenium chromium-treated group) for all groups and was given paracetamol 40 mg/kg body liver enzymes activity. As indicated by the results weight intraperitoneally on 5 day. These groups (2 there were less differences between the treated and 3) were as Controls. and control groups for all enzymes in comparison with that measured 15 and 30 days injection Assay except paracetamol-treated groups.