Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress

• Published in: Human & experimental toxicology Vol. 25; no. 12; pp. 697 - 703
• Main Authors: Teimouri, Fatemeh, Amirkabirian, Nasim, Esmaily, Hadi, Mohammadirad, Azadeh, Aliahmadi, Atousa, Abdollahi, Mohammad
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01.12.2006; Arnold; Sage Publications Ltd
• Subjects: Animals; Biological and medical sciences; Blood Glucose - drug effects; Cells; Cholinesterase Inhibitors - toxicity; Cholinesterases - blood; Diabetes; Diazinon - toxicity; Dose-Response Relationship, Drug; Gluconeogenesis - drug effects; Glucose; Glycogen Phosphorylase, Liver Form - metabolism; Glycogenolysis - drug effects; Hypotheses; Insecticides - toxicity; Lipid Peroxidation - drug effects; Liver; Liver - drug effects; Liver - enzymology; Male; Medical sciences; Metabolism; Oxidation; Oxidative Stress - drug effects; Pesticides; Pesticides, fertilizers and other agrochemicals toxicology; Phosphoenolpyruvate Carboxykinase (GTP) - metabolism; Rats; Rats, Wistar; Risk exposure; Rodents; Thiobarbituric Acid Reactive Substances - metabolism; Toxicology; diazinon; glucose; rat; glycogenolysis; liver; total antioxidant capacity; cell; gluconeogenesis; lipid peroxidation; Oxidative stress; Insecticide; Rat; Toxicity; Liver; Lipids; Glucose; Diazinon; Mechanism of action; Gluconeogenesis; Peroxidation; Digestive system; Pesticides; Rodentia; Detoxification; Antioxidant; Metabolism; Vertebrata; Mammalia; Animal; Organophosphorus compounds
• DOI: 10.1177/0960327106075064
• ISSN: 0960-3271

The aim of this study was to evaluate effects of acute exposure to various doses of diazinon, a widely used synthetic organophosphorus (OP) insecticide on plasma glucose, hepatic cells key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress in rats. Diazinon was administered by gavage at doses of 15, 30 and 60 mg/kg. The liver was perfused and removed under anaesthesia. The activities of glycogen phosphorylase (GP), phosphoenolpyruvate carboxykinase (PEPCK), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were analysed in liver homogenate. Administration of diazinon (15, 30 and 60 mg/kg) increased plasma glucose concentrations by 101.43% (P=0.001), 103.68% (P=0.000) and 160.65% (P=0.000) of control, respectively. Diazinon (15, 30 and 60 mg/kg) increased hepatic GP activity by 43.5% (P=0.05), 70.3% (P=0.00) and 117.2% (P=0.02) of control, respectively. In addition, diazinon (30 and 60 mg/kg) increased hepatic PEPCK by 77.3% (P=0.000) and 93.5% (P=0.000) of control, respectively. Diazinon (30 and 60 mg/kg) decreased liver TAC by 38% (P=0.046) and 48% (P=0.000) of control, respectively. Also diazinon (30 and 60 mg/kg) increased hepatic cell liver lipid peroxidation by 77% (P=0.05) and 280% (P=0.000) of control. The correlations between plasma glucose and hepatic cells TBARS (r2=0.537, P=0.02), between plasma glucose and ChE activity (r2=0.81, P=0.049) and between plasma glucose and hepatic cells GP activity (r2=0.833, P=0.04) were significant. It is concluded that the liver cells are a site of toxic action of diazinon. Diazinon increases glucose release from liver into blood through activation of glycogenolysis and gluconeogenesis as a detoxication non-cholinergic mechanism to overwhelm diazinon-induced toxic stress. The results are in accordance with the hypothesis that OPs are a predisposing factor of diabetes.