title: Effects of methyl mercury on the activity and gene expression of mouse Langerhans islets and glucose metabolism.
abstract: Mercury (Hg) is a well-known heavy metal and causes various toxic effects. It is abundantly present in fish in the form of methyl mercury (MeHg). Also, various other forms of mercury can enter human body either from environment like inhalation or through dental amalgams. The present study was designed to assess MeHg induced toxicity in mouse plasma and pancreatic islets with respect to insulin secretion, oxidative balance, glucose tolerance, gene expression, caspases 3 and 9 activities. MeHg was dissolved in tap water and administered at doses 2.5, 5 and 10 mg/kg/day, for 4 weeks. In mice, MeHg significantly caused increase in plasma insulin as well as C-peptides. Glucose intolerance, insulin resistance and hyperglycemia are main consequences of our study that correlate with the gene expression changes of glucose homeostasis as well. MeHg caused increase lipid peroxidation in a dose-dependent manner in plasma as well as pancreatic islets. In addition, total thiol molecules and ferrous reducing antioxidant power in MeHg treated group was decreased in plasma as well as pancreatic islets. Caspases 3 and 9 activities of pancreatic islets were upregulated in MeHg exposed animals. Reactive oxygen species were extremely high in pancreatic islets of MeHg treated groups. MeHg disrupted gluconeogenesis/glycogenolysis pathways and insulin secretory functions of islets by targeting GDH, GLUT2 and GCK genes of pancreatic islets. In conclusion, the current study revealed that insulin pathways, oxidative balance and glucose metabolism encoded genetic makeup are susceptible to MeHg toxicity and the subsequent oxidative stress and alternations in gene expression could lead toward functional abnormalities in other organs.
authors.affiliation: International Campus, Tehran University of Medical Sciences (TUMS-IC), Tehran, Iran; Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Faheem
authors.initials: F
authors.lastname: Maqbool
authors.affiliation: Department of Pharmacy, Kohat University of Science and Technology, Kohat, 26000, Pakistan.
authors.forename: Haji
authors.initials: H
authors.lastname: Bahadar
authors.affiliation: International Campus, Tehran University of Medical Sciences (TUMS-IC), Tehran, Iran; Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Kamal
authors.initials: K
authors.lastname: Niaz
authors.affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahban
authors.initials: M
authors.lastname: Rahimifard
authors.affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Navaei-Nigjeh
authors.affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyedeh Farnaz
authors.initials: SF
authors.lastname: Ghasemi-Niri
authors.affiliation: International Campus, Tehran University of Medical Sciences (TUMS-IC), Tehran, Iran; Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran. Electronic address: Mohammad.Abdollahi@UToronto.Ca.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008767:Methylmercury Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053148:Caspase 3; C004925:methylmercuric chloride
keywords: Food contaminant; Gene expression; Glucose homeostasis; Insulin resistance; Mercury; Oxidative stress; Toxicity