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 lipid peroxides) production. MDA was determined using the thiobarbituric acid reaction. Rats underwent a 4-day treatment of FK506 (FK, 1 mg/kg 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. Immunosuppressant pretherapy significantly stimulated BrdU uptake by hepatocytes, in association with increased MDA production, while there were no differences in serum liver injury parameters among the groups given or not given immunosuppressants. The implications of the rising MDA values during 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 effective for up-regulation of liver regeneration.
Kim
Y I
YI
Department of Surgery I, Oita Medical University, Japan.
Kobayashi
M
M
Egashira
T
T
Kawano
K
K
Morimoto
A
A
Kai
T
T
Shimada
T
T
D000818:Animals; D001379:Azathioprine / Q000494:pharmacology*; D002455:Cell Division; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D005260:Female; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism*; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances; D015854:Up-Regulation
D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D016572:Cyclosporine; D004247:DNA; D001379:Azathioprine; D016559:Tacrolimus