title: Biochemical evidence on the potential role of organophosphates in hepatic glucose metabolism toward insulin resistance through inflammatory signaling and free radical pathways.
abstract: Several studies show that organophosphate pesticides exert several effects on glucose homeostasis. The current study investigates the influence of subchronic exposure to malathion (MT) on hepatic gluconeogenesis in relation to acetyl cholinesterase (AChE) inhibition, oxidative stress and inflammatory response in the rat. MT was administered by gavage at doses of 25, 50 and 100 mg/kg for 32 days. Fasting hyperglycemia was seen in line with an increased activity of hepatic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and tumor necrosis factor α. In addition to the impaired glucose tolerance and inhibition of AChE in a dose-dependent manner, there were significant increases in hepatic lipid peroxidation, carbonyl groups and 8-deoxyguanosine as the biomarkers of reactive oxygen species-mediated damage to lipid, protein and DNA, respectively. Altered quality of the liver in glucose production especially gluconeogenesis could be a compensatory mechanism against MT toxicity or even result in tissue damage. MT-induced insulin resistance in the liver occurs through oxidative and inflammatory signaling pathways.
authors.affiliation: Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran. mohammad.abdollahi@utoronto.ca
authors.forename: Sara
authors.initials: S
authors.lastname: Mostafalou
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Eghbal
authors.forename: Amir
authors.initials: A
authors.lastname: Nili-Ahmadabadi
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism*; D002800:Cholinesterase Inhibitors; D005609:Free Radicals / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects; D018149:Glucose Intolerance; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006943:Hyperglycemia / Q000503:physiopathology; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008294:Malathion / Q000633:toxicity; D008297:Male; D010755:Organophosphates / Q000633:toxicity*; D018384:Oxidative Stress; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002800:Cholinesterase Inhibitors; D005609:Free Radicals; D010755:Organophosphates; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000110:Acetylcholinesterase; D005952:Glucose-6-Phosphatase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D008294:Malathion