Heat-shock preconditioning reduces oxidative protein denaturation and ameliorates liver injury by carbon tetrachloride in rats

Membrane lipids and cytosolic proteins are major targets of oxidative injur y. This study examined the effect of heat-shock preconditioning associated with the induction of heat-shock protein 72 on liver injury, from the aspec t of lipid peroxidation and protein denaturation after carbon tetrachloride (CCl4) administration in rats - one of the representative oxidative injuri es. Male Wistar rats were divided into two groups, group HS (preconditioned by heat exposure) and group C (not preconditioned). Expression of HSP72 in the liver tissue was confirmed by Western blot analysis, After a 48-h reco very period, all rats were given CCl4 intragastrically. Liver damage was as sessed by measuring serum liver-related enzyme levels and adenine nucleotid e concentration in the liver tissue. Lipid peroxidation and protein denatur ation were evaluated by measuring tiobarbituric acid reactive substances (T BARS) and by immunohistochemical staining of 4-hydroxy-2-nonenal(HNE)-modif ied proteins in the liver. Survival rates of the rats after CCl4 administra tion were also compared. Expression of HSP72 was clearly detected in group HS, but not in group C. Heat-shock preconditioning significantly improved t he survival rate, suppressed the increase in liver-related enzyme levels an d maintained adenosine triphosphate levels (P<0.01 each). HNE-modified prot eins - denatured proteins by free radical attack - were significantly less stained in group HS than in group C (P<0.05). However, TEARS levels did not differ between groups. Because heat-shock preconditioning did not alter TE ARS levels but reduced HNE-modified proteins in association with the expres sion of HSP72, it is suggested that HSP72 did not prevent lipid peroxidatio n but decreased the lipid peroxidation-induced denaturation of proteins. Th is seemed to be a mechanism of heat-shock pre conditioning to ameliorate ox idative liver injury.