RESUMO
Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-ß indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/imunologia , Fígado Gorduroso/imunologia , Inflamação/induzido quimicamente , Resistência à Insulina , Malation/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/imunologia , Citocinas/metabolismo , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Dose Máxima Tolerável , Ratos , Ratos WistarRESUMO
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 (200mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2h 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-1ß, interleukin-6 and interferon-γ 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-1ß, IL-6, INF-γ 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.