PROTECTIVE EFFECTS OF AGED GARLIC EXTRACT AGAINST BROMOBENZENE TOXICITY TO PRECISION CUT RAT-LIVER SLICES

Precision-cut liver slices from phenobarbital-treated rats were incuba ted for up to 8 h with the industrial solvent and hepatotoxin bromoben zene at a final concentration of 1 mM. Phenobarbital pretreatment pote ntiates bromobenzene hepatotoxicity by inducing those P450 isoforms re sponsible for the formation of the active hepatotoxin, namely bromoben zene-3,4-oxide, A reduction in cell viability was indicated by a decre ase in the K+, ATP and glutathione content of the slices and the incre ased release of the intracellular enzymes, lactate dehydrogenase and a lanine aminotransferase. into the medium, Furthermore, levels of lipid peroxidation as judged by the formation of thiobarbituric acid reacti ve substances, were increased approximately 5-fold. Aged garlic extrac t (AGE) at concentrations of 1-5% (v/v) reduced the toxicity of bromob enzene in a concentration-dependent manner as judged by all of the par ameters 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 c ytochrome P450 when assayed as both 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities, but even the highest conc entration used inhibited both activities by less than 50%. It is sugge sted that the hepatoprotective effects of AGE are due primarily to the reduced glutathione-sparing properties of its constituents, most prob ably its organosulphur compounds. (C) 1998 Elsevier Science Ireland Lt d. All rights reserved.