Advances in Life Science and Technology www.iiste.org ISSN 2224-7181 (Paper) ISSN 2225-062X (Online) DOI: 10.7176/ALST Vol.75, 2019 23 Induction of Oxidative Stress: A Possible Mechanism for the Arsenic Induced Catastrophes in Male Wistar Rats John Olabode Fatoki 1 Jelili Abiodun Badmus 1 Comfort Oluwatoyin Fatoki 2 Adeniran Sanmi Adekunle 1 Gbadebo Emmanuel Adeleke 1 * Samuel Abiodun Kehinde 3 1.Department of Biochemistry, Faculty of Basic Medical Sciences, Ladoke Akintola University of Technology, Ogbomoso, Nigeria 2.Department Microbiology, Faculty of Basic and Applied Sciences, Osun State University, Osogbo, Nigeria 3.Department of Biochemistry, College of Biosciences, Federal University of Agricultural, Abeokuta, Nigeria *Corresponding author: Gbadebo Emmanuel Adeleke: geadeleke@lautech.edu.ng Abstract Arsenic is an environmental pollutant and its contamination in the drinking water is considered as a serious worldwide environmental health threat. The present study investigated the effects of arsenic exposure on antioxidant parameters and p53 expression in male albino rats. The animals (n=45) were exposed to arsenic (100 ppm, 150 ppm and 200 ppm) for 4, 8 and 12 weeks as sodium arsenate in drinking water. Control animals (n=15) received distilled water for the same period. Hepatic superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), reduced glutathione (GSH), lipid peroxidation and total protein were evaluated spectrophotometrically. Expression of p53 was also detected by histochemical staining. Before the commencement of arsenic exposure, five animals were sacrificed to obtain baseline data. ANOVA followed by Tukey’s test was used to analyse the results with p<0.05 considered significant. Significant decrement in hepatic activities of SOD, catalase and GPx as well as hepatic concentration of GSH and total protein concentration characterized exposure to all the dose regimens of inorganic arsenic at all the time interval. Corroboratively, significant elevation was observed in malondialdehyde (MDA). The expression of p53 decreased in the groups that were exposed to arsenic as compared to the control animals. The findings from the present study suggests excessive generation of free radicals and reduction in p53 expression in arsenic – induced hepatotoxicity. Keywords: Arsenic, Toxicity, Antioxidants, Lipid peroxidation DOI: 10.7176/ALST/75-04 Publication date:June 30 th 2019 1. Introduction Arsenic is a toxic metalloids, it exists in +5, +3, 0, and -3 oxidation states. It also exists in both organic and inorganic form in the environment. Arsenic in these four oxidation states is widely and ubiquitously distributed in the environment as a results of natural and anthropogenic activities in the environment. The +5 (arsenate) and +3 (arsenite) oxidation states are the most common forms of the natural occurring arsenic in the environment (Obinaju, 2009; Mateos et al., 2010, satyapal et al., 2018). The major cause of arsenic toxicity in human is due to exposure to contaminated drinking water from natural geological sources as most countries of the world have their drinking water contaminated with arsenic (Gebel, 2000; Matschullat, 2000; Zaw & Emett, 2002). Apart from drinking contaminated water, other form of exposure includes but not limited to; inhalation, absorption through the skin. Arsenicals may also enter food chain from agricultural products (Ratnaike, 2003). The major absorption site of arsenic in human is the ileum by an electrogenic process involving a proton gradient (Ratnaike & Barbour 2000), and are deposited in the skin, lungs, kidney, liver and heart. Lower amount of arsenic has however been reported have been observed in the muscles and neuronal tissues (Klaassen, 1996). Meanwhile, Flora et al. (2007) also reported that prolong exposure to arsenic for two to four weeks can also cause its incorporation into the nails and hair by binding to sulfhydryl groups of keratin. Arsenic inactivates approximately 200 enzymes involved in many important metabolic reactions such as cellular energy metabolism and DNA replication and repair with concomitant induction of plethora of diseases by oxidative stress, altered DNA methylation, altered DNA repair, mitochondrial damage, uncontrolled cell proliferation leading to promotion of tumourigenesis. Arsenicals can also substituted for phosphate in high energy compound such as ATP with concomitant consequences on energy metabolism of the cell (Ratnaike, 2003; Butt & Rehman, 2011). The overall effectiveness of the electron transport chain notwithstanding, a small amount of electrons leak out of the respiratory chain and can therefore partially reduce oxygen to form reactive oxygen species (ROS) such as O2., H2O2 and – OH (Finsterer & Ohnsorge, 2013). These ROS are generated in normal cellular metabolism and signal transduction (Zhang et al., 2014). They can however cause oxidative damage to cellular macromolecules such as nucleic acids, proteins and lipids (Pace et al., 2017). Innate antioxidants such as SOD, catalase and glutathione peroxidase are the first line of defense against ROS effects. An amplified mitochondrial production of ROS and/or reduced intrinsic antioxidant capacity leads to an increased oxidative stress and are linked with a multitude of downstream effects as well as disease initiation and progression (Moskovitz et al.,