Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats

Aims: Occupational exposure to organophosphate pesticides is becoming a common and increasingly alarming world-wide phenomenon. The present study is designed to investigate the preventive effect of N-acetylcysteine on malathion-induced hepatic injury and inflammation in rats. Main methods: Adult male Wistar rats of body weight 200-230 g were used for the study. Malathion (200 mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2 g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2 h after the last administration. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate desyhdogenase), inflammation (leukocyte counts, myeloperoxidase, immunophenotyping of CD4(+) and CD8(+), interleukin-1 beta, interleukin-6 and interferon-gamma expression) and oxidative stress (lipid peroxidation, reduced glutathione and antioxidant status) were assessed. Key findings: Malathion induced an increase in activities of hepatocellular enzymes in plasma, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) percent and pro-inflammatory cytokines, when decreased antioxidant status in liver was noted. When malathion-treated rats were compared to NAC supplemented rats, leukocytosis, T cell count and IL-1 beta, IL-6, INF-gamma expression were reduced. Furthermore, NAC restored liver enzyme activities and oxidative stress markers. Significance: Malathion induces hepatotoxicity, oxidative stress and liver inflammation. N-acetylcysteine showed therapeutic effects against malathion toxicity. (C) 2014 Elsevier Inc. All rights reserved.