title: The molecular mechanisms of liver and islets of Langerhans toxicity by benzene and its metabolite hydroquinone in vivo and in vitro.
abstract: Benzene (C6H6) is one of the most commonly used industrial chemicals causing environmental pollution. This study aimed to examine the effect of benzene and its metabolite hydroquinone on glucose regulating organs, liver and pancreas, and to reveal the involved toxic mechanisms, in rats. In the in vivo part, benzene was dissolved in corn oil and administered through intragastric route at doses of 200, 400 and 800 mg/kg/day, for 4 weeks. And, in the in vitro part, toxic mechanisms responsible for weakening the antioxidant system in islets of Langerhans by hydroquinone at different concentrations (0.25, 0.5 and 1 mM), were revealed. Benzene exposure raised the activity of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) enzymes and increased fasting blood sugar (FBS) in comparison to control animals. Also, the activity of hepatic glucokinase (GK) was decreased significantly. Along with, a significant increase was observed in hepatic tumor necrosis factor (TNF-α) and plasma insulin in benzene treated rats. Moreover, benzene caused a significant rise in hepatic lipid peroxidation, DNA damage and oxidation of proteins. In islets of Langerhans, hydroquinone was found to decrease the capability of antioxidant system to fight free radicals. Also, the level of death proteases (caspase 3 and caspase 9) was found higher in hydroquinone exposed islets. The current study demonstrated that benzene and hydroquinone causes toxic effects on liver and pancreatic islets by causing oxidative impairment.
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Haji
authors.initials: H
authors.lastname: Bahadar
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Faheem
authors.initials: F
authors.lastname: Maqbool
authors.affiliation: b School of Pharmacy, Ardabil University of Medical Sciences , Ardabil , Iran , and.
authors.forename: Sara
authors.initials: S
authors.lastname: Mostafalou
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Mahdi
authors.initials: M
authors.lastname: Gholami
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .
authors.forename: Elmira
authors.initials: E
authors.lastname: Ghafour-Boroujerdi
authors.affiliation: a Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center , International Campus, Tehran University of Medical Sciences , Tehran , Iran .|c Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006873:Hydroquinones / Q000633:toxicity*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D006873:Hydroquinones; D007328:Insulin; D001554:Benzene; C031927:hydroquinone
keywords: Benzene; environmental pollutants; glucose homeostasis; hydroquinone; oxidative stress