A comparative study on toxicity induced by carbosulfan and malathion in Wistar rat liver and spleen.

Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this comparative study, we investigated the effect of subchronic exposure of OPs (malathion, MAL) and CM (Carbosulfan, CB) on rat liver and spleen. Biochemical analysis showed that levels of hepatic enzymes (ALT, ALP, LDH and PAL) changed after exposure to the pesticides. In the liver extracts, lipid peroxidation index increased after the treatment by pesticides. Our results indicated that exposure to MAL and CB leads to alteration of liver redox status. Both pesticides induced focal inflammation and fibrosis in the liver. After subchronic administration of MAL (200 mg/kg) and CB (25 mg/kg), systemic inflammation, as depicted by the increase in IFN-δ activity in liver, was observed in both malathion and carbosulfan treated animals. In addition, the results showed that MAL significantly increased TCD4+ and TCD8+ lymphocyte number. It also decreased INF-δ and IL-4 production. However, CB induced a reduction of TCD8+ number and cytokine production in spleen cells. In conclusion, malathion and carbosulfan had significant immunomodulatory properties in the spleen with inflammation and oxidative stress induction in the liver.

Carbosulfan-induced oxidative damage following subchronic exposure and the protective effects of N-acetylcysteine in rats.

Carbosulfan (CB)-induced oxidative stress leads to the inevitable accumulation of free radicals and eventual alteration of antioxidant enzymes in various biological systems. The present study is designed to investigate the preventive effect of N-acetylcysteine (NAC) on carbosulfan-induced hepatic and renal dysfunction in rats. Rats exposed to CB and NAC were examined for toxicity by assessing various biochemical alteration and stress markers including in liver and kidney. Significant increases of blood alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), creatinine and urea were detected in CB-treated rats. In addition, the levels of antioxidative enzymes such as catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) also were assessed. According to the results, rats exposed to carbosulfan showed a significant increase in the accumulation of stress markers and an alteration in the antioxidative enzymes activity, when compared to their respective controls. Interestingly, administration of NAC to CB-treated rats attenuates the toxicity of this compound, objectified by biochemical and oxidative improvement of liver and kidney. Thus, the present study reports for the first time that NAC could be a promising therapeutic agent against CB induced oxidative stress.

Disruption of steroidogenesis after dimethoate exposure and efficacy of N-acetylcysteine in rats: an old drug with new approaches.

Organophosphates (OPs) like dimethoate (DMT), are pesticides used worldwide, which can affect both animals and human. Whereas their toxicity is due to acetylcholinesterase inhibition, their secondary toxic effects have been related to free oxygen radical biosynthesis. The present study was designed to investigate the reprotoxic effects of DMT and the protective role of N-acetylcysteine (NAC) in male rat. DMT (20 mg/ kg/body weight) was administered daily to rats via gavage in corn oil and NAC (2 g/l) was added to drinking water for 30 days. Rats were sacrificed on the 30th day, 2 h after the last administration. Markers of testis injury (steroidogenesis impairment) and oxidative stress (lipid peroxidation, reduced glutathione, and antioxidant status) were assessed. In DMT-exposed rats, the serum level of testosterone was decreased. Further, a significant increase in lipid peroxidation level and a significant decrease in the activities of antioxidant enzymes were observed in the testis of rats during DMT intoxication. Real-time PCR (RT-PCR) analysis demonstrated a decrease in messenger RNA (mRNA) levels for testicular steroidogenic acute regulatory StAR protein, cytochrome P450scc, 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and 17ß hydroxysteroid dehydrogenase (17ß-HSD) in the testis after DMT exposure. No significant changes in the oxidative stress status and selected reproductive variables were observed on CTN group, whereas NAC restored the oxidative stress and the steroidogenesis on NAC group. Dimethoate induces reprotoxicity and oxidative stress. N-acetylcysteine showed therapeutic recovery effects against dimethoate toxicity.