Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats

Environ Toxicol Pharmacol. 2014 Sep;38(2):542-53. doi: 10.1016/j.etap.2014.08.007. Epub 2014 Aug 18.

Abstract

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-β 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.

Keywords: Hepatosteatosis; Inflammation; Insulin resistance; Malathion; Oxidative stress.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Chemical and Drug Induced Liver Injury / immunology*
  • Chemical and Drug Induced Liver Injury / pathology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Fatty Liver / chemically induced
  • Fatty Liver / immunology*
  • Fatty Liver / pathology
  • Gene Expression Regulation / drug effects
  • Inflammation / chemically induced*
  • Insulin Resistance*
  • Lipid Peroxidation / drug effects
  • Malathion / toxicity*
  • Male
  • Maximum Tolerated Dose
  • Oxidative Stress / drug effects*
  • Pesticides / toxicity*
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Pesticides
  • Malathion