Time – Course of Sodium Arsenate Induced Hepatotoxicity and Nephrotoxicity in Male Wistar Rats

John O Fatoki ,Jelili A Badmus ,Samuel Abiodun Kehinde ,Ot Afolabi ,O T Adedosu ,Adeniran Sanmi Adekunle ,G E Adeleke

doi:10.7176/jnsr/9-4-09

Abstract

Arsenic exposure has been implicated by several epidemiological studies as an important metalloid that is currently poisoning millions of people globally. In order to investigate the time – course of arsenic exposure on hepatic and renal toxicity, male albino rats (n=45) were exposed to arsenic (100 ppm, 150 ppm and 200 ppm) for 4, 8 and 12 weeks as sodium arsenate in their drinking water. Control animals (n=15) received distilled water for the same period after which blood and vital organs were removed from the animals and analyzed for alanine amino transaminase (ALT), aspartate amino transaminase (AST) gamma amino transaminase (γGT), alkaline phosphatase (ALP), creatinine and urea spectrophotometrically. Histological changes in hepatocytes was also examined. Before the commencement of arsenic exposure, five animals were sacrificed to obtain baseline data. Significant elevation in plasma ALT, AST, γGT and alkaline phosphatase activities characterized the effect of the arsenical at all doses and time interval relative to the controls. Plasma levels of creatinine and urea were also elevated at all-time intervals in the arsenic group. In most of the cases observed, the elevated level of these biochemical marker in circulation are time – and dose – dose dependent. Hepatic histopathology reveals degeneration of cytoplasmic contents, evidence of necrosis, collapse of central vein, cytoplasmic inclusion and enlarged hepatic sinusoids in arsenic – exposed groups. These findings suggest that different dose regimens of sodium arsenate at different time interval caused degenerative changes in hepatic and renal tissues in rats in dose – and time – dependent fashion. Keywords: Arsenic, Time – course, Hepatotoxicity, Nephrotoxicity DOI: 10.7176/JNSR/9-4-09

Highlights

Increasing human activities have led to the contamination of air, water, soil and food especially with the toxic, non-essential elements such as arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) (Clarkson, 1995)
The inorganic arsenic is methylated to monomethylarsonic acid (MMA) and to dimethylarsenic acid (DMA) and this metabolism is followed by urinal excretion
The results from the present study demonstrated that exposure of rats to pentavalent inorganic arsenic through the drinking water could be associated with hepatic and renal toxicities

Summary

Introduction

Increasing human activities have led to the contamination of air, water, soil and food especially with the toxic, non-essential elements such as arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) (Clarkson, 1995) Among these metals, arsenic, a ubiquitous metalloid, exhibits a complex metabolism and is possibly the most abundant pollutant (Hu, 2000; Pradosh & Anupama, 2000). Www.iiste.org microcirculation, peripheral artery disorder coronary heart disease (CHD), stroke and various forms of cancer (Wang et al, 2006; States et al, 2009; Hughes et al, 2011; Mazumder & Dasgupta, 2011) All these arsenic – induced toxicity depend on many factors such as valence state, form (either organic or inorganic), particle size, solubility, rates of absorption and elimination (ATSDR, 2007). Despite volumes of scientific findings about the toxic effects of arsenic, the time – course and possible mechanisms involved in arsenic – induced toxicity following acute and chronic arsenic exposure, as well as the threshold for biologic effects and disease risks remain enigmatic(Hughes et al, 2011).The present study focused on the time – course of arsenic-induced hepatotoxicity and nephrotoxicity

Animals and treatment

Biochemical Assay

Histopathology

Results

Discussion

Conclusion