AUGMENTATION OF HEPATOCYTE PROLIFERATION BY IMMUNOSUPPRESSANT PRETHERAPY IS ASSOCIATED WITH UP-REGULATION OF MALONDIALDEHYDE PRODUCTION

We studied the relationship between augmentation of liver regeneration with immunosuppressants and malondialdehyde (MDA, an end-product of l ipid peroxides) production. MDA was determined using the thiobarbituri c acid reaction. Rats underwent a 4-day treatment of FK506 (FK, 1 mg/k g per day), cyclosporine (Cs, 10 mg/kg) or azathioprine (AZA, 1 mg/kg) by gavage prior to 70% hepatectomy. They were then divided into four groups: (1) controls ( vehicle-treated); (2) FK; (3) Cs; (4) AZA. MDA levels, uptake of BrdU (5-bromo-2-deoxyuridine) in the liver and serum biochemistry were investigated 24 h after hepatectomy. Immunosuppress ant pretherapy significantly stimulated BrdU uptake by hepatocytes, in association with increased MDA production. while there were no differ ences in serum liver injury parameters among the groups given or not g iven immunosuppressants. The implications of the rising MDA values dur ing liver regeneration are discussed with respect to immunosuppression and a measure of lipid peroxidation. Additional study indicated that one immunodepressant pretreatment (24 h prior to hepatectomy) was effe ctive for up-regulation of liver regeneration.