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), a nd malic enzyme (ME) were studied in rat liver when necrosis and regen eration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12-24 hr of trea tment and increased thereafter. These biphasic changes are related to the sequential processes of liver injury and hepatocellular regenerati on. Expression of mRNA for G6PDH decreased at 12 hr following thioacet amide 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 a nd increased during the postnecrotic regenerating process, reaching on ly half of the control value at 96 hr. A relationship between mRNA G6P DH gene expression, oxidative stress (detected by the GSH/GSSG ratio a nd malondialdehyde (MDA) concentration), and DNA synthesis is proposed .