Protective effects of aged garlic extract against bromobenzene toxicity to precision cut rat liver slices.
Precision-cut liver slices from phenobarbital-treated rats were incubated for up to 8 h with the industrial solvent and hepatotoxin bromobenzene at a final concentration of 1 mM. Phenobarbital pretreatment potentiates bromobenzene hepatotoxicity by inducing those P450 isoforms responsible for the formation of the active hepatotoxin, namely bromobenzene-3,4-oxide. A reduction in cell viability was indicated by a decrease in the K+, ATP and glutathione content of the slices and the increased release of the intracellular enzymes, lactate dehydrogenase and alanine aminotransferase, into the medium. Furthermore, levels of lipid peroxidation as judged by the formation of thiobarbituric acid reactive substances, were increased approximately 5-fold. Aged garlic extract (AGE) at concentrations of 1-5% (v/v) reduced the toxicity of bromobenzene in a concentration-dependent manner as judged by all of the parameters of viability studied, with the exception of lipid peroxidation which was reduced to control levels even at the lowest concentration of garlic extract used. AGE was found to cause partial inhibition of cytochrome P450 when assayed as both 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities, but even the highest concentration used inhibited both activities by less than 50%. It is suggested that the hepatoprotective effects of AGE are due primarily to the reduced glutathione-sparing properties of its constituents, most probably its organosulphur compounds.
School of Biomolecular Sciences, Liverpool John Moores University, UK.
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Wang
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Zuzel
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Rahman
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Billington
D015660:7-Alkoxycoumarin O-Dealkylase / Q000096:biosynthesis; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism / Q000633:toxicity*; D046508:Culture Techniques; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005737:Garlic; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D001969:Bromobenzenes; D010936:Plant Extracts; D017392:Thiobarbituric Acid Reactive Substances; C043067:bromobenzene 3,4-oxide; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; C032036:bromobenzene; D007770:L-Lactate Dehydrogenase; D015660:7-Alkoxycoumarin O-Dealkylase; D019362:Cytochrome P-450 CYP2B1; D000410:Alanine Transaminase; D005978:Glutathione; D011188:Potassium