Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo |
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| Authors: | O Strubelt M Younes R Pentz |
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| Affiliation: | 1. Department of Science and Technology, Tay Nguyen University, Buon Ma Thuot 630000, Viet Nam;2. Department of Chemistry, Tamkang University, New Taipei 25137, Taiwan;3. Life Science Development Center, Tamkang University, New Taipei 25137, Taiwan;1. Department of Biological Chemistry, Regional University of Cariri, Crato, CE, 63105-000, Brazil;2. Department of Physics, Federal University of Ceará, Fortaleza, CE, 60455-760, Brazil;3. Science and Technology Centre – Course of Physics, State University of Ceará, Quixadá, CE, 62040-370, Brazil;4. Institute of Physics, Federal University of Mato Grosso, Cuiabá, MT, 78060-900, Brazil;1. University of Gastronomic Sciences, Piazza Vittorio Emanuele 9, I-12060 Pollenzo, Italy;2. Estonian Literary Museum, Vanemuise 42, Tartu 51003, Estonia;3. Department of Dermatology, Emory University School of Medicine, 615 Michael St., Whitehead 105-L, Atlanta, GA 30322, USA;4. Center for the Study of Human Health, Emory College of Arts and Sciences, 550 Asbury Circle, Candler Library 107, Atlanta, GA 30322, USA;5. Institute for Biological and Environmental Research, University of Prishtina “Hasan Prishtina”, Mother Teresa Str., 10000 Prishtinë, Republic of Kosovo;1. Environmental Chemistry, Federal University of Tocantins, UFT, Gurupi, TO, 77402-970, Brazil;2. Chemistry Institute, Department of Organic Chemistry, São Paulo State University, UNESP, Araraquara, SP, 14800-900, Brazil;3. São Carlos Institute of Chemistry, University of São Paulo, USP, CP 780, São Carlos, SP, 13560-970, Brazil;4. Departamento de Química, Grupo de Cromatografa de Bioafnidade e Produtos Naturais, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto, SP, 14040-901, Brazil;5. Institute of Botany - Plant Biochemistry and Physiology Section, São Paulo, SP, 01061-970, Brazil;6. Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, UNESP, Araraquara, SP, 14800-903, Brazil;7. Departamento de Biofísica e Fisiologia, Laboratório de Cancerologia Experimental,Universidade Federal do Piauí, UFPI, Teresina, PI, 64049-550, Brazil;1. Department of Food Chemistry, Technology and Biotechnology, Gdańsk University of Technology, Gdańsk, Poland;2. Department of Analytical Chemistry, Gdańsk University of Technology, Gdańsk, Poland |
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| Abstract: | Ethanol at initial concentrations between 0.75 and 6 g/l produced a dose-dependent release of the enzymes glutamic-pyruvic-transaminase and sorbitol dehydrogenase (GPT, SDH) from the isolated perfused rat liver. At the concentration of 6 g/l, it also decreased the oxygen consumption and elevated the calcium content of the isolated livers. These toxic effects of ethanol were significantly enhanced in livers, the glutathione content of which had been depleted by pretreatment with phorone. Ethanol-induced toxicity in glutathione-depleted isolated livers could be prevented both by inhibition of alcohol dehydrogenase with 4-methylpyrazole and of xanthine oxidase with allopurinol. In rats, in vivo, 1.6 g/kg ethanol injected intravenously produced a small increase in serum GPT and SDH concentrations 4 h after its administration. This increase in enzyme activities was several-fold higher and longer lasting in rats pretreated with phorone. Glutathione depletion per se did not induce hepatotoxicity in vitro or in vivo. Since glutathione is involved in several lines of defense against oxidative damage, our results of an enhanced susceptibility of glutathione-depleted livers to ethanol toxicity favour the hypothesis that ethanol exerts its hepatotoxic action via an activation of molecular oxygen. |
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