Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide.

NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were studied in rat liver when necrosis and regeneration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12-24 hr of treatment and increased thereafter. These biphasic changes are related to the sequential processes of liver injury and hepatocellular regeneration. Expression of mRNA for G6PDH decreased at 12 hr following thioacetamide injection and increased during liver regeneration, reaching its highest levels of expression at 48 hr (247% of the control), parallel to the peak of DNA synthesis. Expression of ME decreased at 12-24 hr and increased during the postnecrotic regenerating process, reaching only half of the control value at 96 hr. A relationship between mRNA G6PDH gene expression, oxidative stress (detected by the GSH/GSSG ratio and malondialdehyde (MDA) concentration), and DNA synthesis is proposed.