Alpha lipoic acid protects against acute hepatocellular damage induced by carbon tetrachloride in vitro: comparison with N-acetylcysteine

ABSTRACT

Alpha lipoic acid [ALA] has been widely investigated as a potentially useful protective and antioxidant agent in various pathological states. Oxidative stress is one of the mechanisms involved in acute carbon tetrachloride [CCI4]-induced hepatotoxicity. In previous in vivo work, ALA has shown a potentially protective effect in acute CCI4-induced hepatotoxicity. The current work was designed to investigate whether this effect could be also manifested in vitro using isolated rat hepatocytes in suspension. This was carried out in comparison with one of the standard hepatoprotective agents viz., N-acetylcysteine [NAC]. Suspended hepatocytes were preincubated with either ALA or NAC for 30 min before being exposed to the hepatotoxin for n further 30 min. The hepatotoxicity was assessed by estimating the leakage of lactate dehydrogenase [LDH], the enhanced formation of lipid peroxides and the depletion of intracellular reduced glutathione [GSH]. ALA showed a protective effect against the induced hepatocellular injury almost identical to NAC, as was evidenced by its inhibitory influence on LDH leakage, the enhanced lipid peroxide production, and depletion of GSH. These data show that the hepatoprotective effect of ALA is effective as NAC in vitro and seems to be mediated, at least in part, by its antioxidant properties