title: Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats.
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.
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: lasram_montassar@yahoo.fr.
authors.forename: Mohamed Montassar
authors.initials: MM
authors.lastname: Lasram
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia; Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: Ines Bini
authors.initials: IB
authors.lastname: Dhouib
authors.affiliation: Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Kahna
authors.initials: K
authors.lastname: Bouzid
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Aicha Jrad
authors.initials: AJ
authors.lastname: Lamine
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
authors.forename: Alya
authors.initials: A
authors.lastname: Annabi
authors.affiliation: Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belhadjhmida
authors.affiliation: Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia.
authors.forename: Malika Ben
authors.initials: MB
authors.lastname: Ahmed
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: salouaelfazaa@tunet.tn.
authors.forename: Saloua El
authors.initials: SE
authors.lastname: Fazaa
authors.affiliation: Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Jaouida
authors.initials: J
authors.lastname: Abdelmoula
authors.affiliation: Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia. Electronic address: najoua.gharbi@planet.tn.
authors.forename: Najoua
authors.initials: N
authors.lastname: Gharbi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects; D008294:Malathion / Q000633:toxicity*; D008297:Male; D020714:Maximum Tolerated Dose; D018384:Oxidative Stress / Q000187:drug effects*; D010575:Pesticides / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D010575:Pesticides; D008294:Malathion
keywords: Hepatosteatosis; Inflammation; Insulin resistance; Malathion; Oxidative stress