Oxid Antioxid Med Sci 2014; 3(2):109-117 ISSN: 2146-8389 http://www.oamsjournal.com 109 ORIGINAL ARTICLE Hepato-renal damage and oxidative stress associated with pirimiphos-methyl exposure in male mice Tarek M. Heikal, Abdel-Tawab H. Mossa, Azza W. Ibrahim, Hala F. Abdel-Hamid Environmental Toxicology Research Unit (ETRU), Pesticide Chemistry Department, National Research Center (NRC), Cairo, Egypt Received April 2, 2014 Accepted May 26, 2014 Published Online June 7, 2014 DOI 10.5455/oams.260514.or.064 Corresponding Author Tarek Mohamed Heikal Environmental Toxicology Research Unit (ETRU), Pesticide Chemistry Department, National Research Centre, El-Behoos St., P.O. Box 12622, Dokki, Cairo, Egypt. tarekhl@yahoo.com Key Words Histopathology; Kidney function; Liver function; Oxidative damage; Pirimiphos-methyl Abstract Objective: For many years, the organophosphorus insecticide pirimiphos-methyl (PM) was used as a valuable tool against several stored-product insect species. However, the knowledge of its toxicity for field applicators, manufacturing workers and public health is very limited in literatures. The present work was therefore undertaken in order to investigate the hepato-renal toxicity associated with PM exposure in mice. Method: Mice were divided into five groups of six mice each and administered PM at doses of 0.03 (ADI), 10 (NOAEL), 31.05 ( 1 /40 LD50) and 62.11 ( 1 /20 LD50) mg/kg body weight in corn oil for 45 days via oral gavage. Result: The results revealed that the activities of serum enzymes alkaline phosphatase, alanine and aspartate aminotransferases, and serum levels of total protein, urea and creatinine were significantly elevated (by 13-63% of control activity), whereas the level of serum albumin was significantly reduced (by 15-21%) following administration of 31.05 and 62.11 mg pirimiphos- methyl/kg body weight. In liver and kidney tissues, level of glutathione and the activity of superoxide dismutase and catalase enzymes were significantly decreased, while the level of lipid peroxidation were significantly increased compared to the control group. The lower doses of (ADI, NOAEL) PM induced insignificant or limited alteration in the above-mentioned biochemical parameters. Histopathological examination revealed hepato-renal cellular damage in all tested doses of PM compared to untreated group. Conclusion: The intensity of the insults in liver and kidney functions as well as oxidative damage represented by biochemical alterations and histopathological findings were demonstrated in a dose-dependent manner. © 2014 GESDAV INTRODUCTION Pesticides are ubiquitous in the environment and have significant economic, environmental and public health benefits by increasing the food production and decreasing the vector-borne diseases [1]. Their initial success was mainly based on their high toxicity, high biological specificity and rapid environmental degradation [2]. Organophosphate (OP) compounds are occasionally used indiscriminately in large amounts causing environmental pollution [3, 4]. Residual amounts of OPs including pirimiphos-methyl have been detected in the soil, water bodies, vegetables, grains and other foods products [2, 5]. However, the health effects caused by this occupational exposure are massive and irreversible in some cases. The widespread use of OPs and the high rates of food contamination could leave humans, animals and birds at high risk of pesticidal toxicity [6, 7]. Organophosphate insecticides represent the most widely group of pesticides that has been shown to have toxic effects to non-target organisms [6-9]. They elicit their extensive toxicities through various mechanisms and pathways. The primary toxicity associated with acute exposure to OP insecticides in humans and animals is the inhibition of acetylcholinesterase (AChE) enzyme [10]. The inhibition of AChE increases the availability of acetylcholine which in turn can stimulate cholinergic receptors producing both nicotinic and muscarinic effects in the organism such as muscle contraction and secretion in many glands [11]. However, they also elicit their toxicities via other mechanisms including cytotoxicity, genotoxicity, immunotoxicity, delayed polyneuropathy, nephrotoxi- city, hepatotoxicity, carcinogenicity and reproductive toxicity [11-19]. Furthermore, OP insecticides induced toxic effects that probably occur through the generation of reactive oxygen species (ROS), causing damage to various membranous components of the cell [20]. Pirimiphos-methyl (PM; O-[2-(Diethylamino)-6- methylpyrimidin-4-yl] O,O-dimethyl phosphorothioate) is one of the most commonly used grain protectants globally. It is an OP compound, with a wide margin of safety to mammals and a broad spectrum of insecticidal activity [21]. Arthur et al [22] declared that PM has been on the market for many years and used as a valuable tool against several stored-product insect species. It is rapidly absorbed, metabolized and