Evaluation of the nephrotoxic effects of insecticide diazinon in rats

Muhammad Dawood Shah, (2011) Evaluation of the nephrotoxic effects of insecticide diazinon in rats. Masters thesis, Universiti Malaysia Sabah.

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Abstract

Oxidative damage of biomolecules is implicated in the pathogenesis of various renal inJuries. Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothioate), an organophosphate insecticide, has been used worldwide in agriculture and domestically for several years, which has led to a variety of negative effects in non target species including humans and therefore, are cause of concern. There are few studies on diazinon with reference to its toxicity in kidney on exposure to low doses based on LD50. The possible toxicity of diazinon is assumed to be as a result of induction of oxidative stress, however, there are not enough studies to confirm this as a result of exposure to low doses of diazinon for acute, subacute and chronic periods. Therefore, the present study was conducted to analyze the direct toxic effects of diazinon which caused biochemical and ultrastructural changes and to evaluate its mechanism of action with special reference to its possible reactive oxygen species generating potential (ROS) in kidney with acute, subacute and chronic exposure in rat models. Adult Sprague Dawley male rats were treated with diazinon in corn oil orally (gavage) according to the selected doses (10 mg/kg body weight, 15 mg/kg body weight and 30 mg/kg body weight) for 7, 14 and 56 consecutive days. The selection of dose regimen of diazinon was based on previously published data which indicate substantial alterations in many biochemical parameters. All of these animals were sacrificed 24 h after the last dose of diazinon or saline within a period of 1 h. Blood and kidney tissues of these animals were taken quickly. Kidneys were cleaned free of extraneous material and perfused immediately with ice cold saline (0.85% w/v, sodium chloride) for biochemical and histopathological studies to assess the derangement in the functioning of kidney. Body weight decreased Significantly in diazinon treated group compared to the saline treated control. Treatment of rats with diazinon induces oxidative stress in kidney, as evident by significant induction in lipid peroxidation (TBARS) which is accompanied by depletion of enzymatic and non-enzymatic antioxidant molecules (viz. GPx-glutathione peroxidase; GR-glutathione reductase; GST glutathione S-transferase; G6PD-glucose 6-phosphate dehydrogenase; CAT-catalase; GSH-reduced glutathione). In contrast, activities of renal y-glutamyl transpeptidase (yGGT) and quinone reductase (QR) were increased significantly. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen (BUN) and serum creatinine (CRN). Additionally, histopathological examinations showed extensive renal injuries, characterized by nuclear pycnosis, kidney swelling with obliteration of space in Bowman's capsule, degeneration of tubular epithelial cells, necrosis of proximal tubules, flattened epithelium and congested blood vessels. Reviewing all observations, our results indicate that diazinon treatment eventuates in decreased renal glutathione, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.

Item Type:Thesis (Masters)
Uncontrolled Keywords:rat, insecticide diazinon, toxicity, chronic period, biochemical, nephrotoxic, kidney, oxidative stress, antioxidant enzyme
Subjects:R Medicine > RC Internal medicine
Divisions:SCHOOL > Biotechnology Research Institute (BRI)
ID Code:6528
Deposited By:IR Admin
Deposited On:10 Jul 2013 14:35
Last Modified:10 Jul 2013 14:35

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