Metadoxine prevents damage produced by ethanol and acetaldehyde in hepatocyte and hepatic stellate cells in culture

Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to improv e liver function tests in alcoholic patients. In the present work we have i nvestigated the effect of metadoxine on some parameters of cellular damage in hepatocytes and hepatic stellate cells in culture treated with ethanol a nd acetaldehyde. HepG2 and CFSC-2G cells were treated with 50 mM ethanol or 175 muM acetaldehyde as initial concentration in the presence or absence o f 10 mug ml(-1) of metadoxine. Twenty-four hours later reduced and oxidized glutathione content, lipid peroxidation damage, collagen secretion and IL- 6, IL-8 and TNF-alpha secretion were determined. Our results suggest that m etadoxine prevents glutathione depletion and the increase in lipid peroxida tion damage caused by ethanol and acetaldehyde in HepG2 cells. In hepatic s tellate cells, metadoxine prevents the increase in collagen and attenuated TNF-alpha secretion caused by acetaldehyde. Thus, metadoxine could be usefu l in preventing the damage produced in early stages of alcoholic liver dise ase as it prevents the redox imbalance of the hepatocytes and prevents TNF- alpha induction, one of the earliest events in hepatic damage. (C) 2001 Aca demic Press.