Beneficial effects of cyclosporine on postischemic liver injury in rats.
The discovery of cyclosporine has had a significant impact on preventing the rejection of transplanted organs in humans. In this study, we present another positive aspect of cyclosporine. Rats were pretreated with cyclosporine (10 mg/kg, i.v.), or untreated. After 2-hr ischemia or 1 hr of reperfusion following 2-hr ischemia, livers were isolated and liver adenine nucleotide concentrations were determined. Liver mitochondria were prepared and their function was estimated polarographically. Leakage of AST, ALT, LDH, and adenine nucleotides into the hepatic vein just after reperfusion was also measured. Cyclosporine treatment did not affect ischemia-induced mitochondrial dysfunction, nor did it prevent the associated decrease in adenosine triphosphate concentration. However, treatment with cyclosporine accelerated the recovery of mitochondrial function and of tissue adenosine triphosphate concentrations. Cyclosporine treatment also mitigated leakage of AST, ALT, LDH, and adenine nucleotides after reperfusion. These results indicate that cyclosporine shows a potent protective effect on ischemia-reperfusion-related liver injury.
Kurokawa
T
T
Department of Surgery II, Nagoya University School of Medicine, Japan.
Kobayashi
H
H
Nonami
T
T
Harada
A
A
Nakao
A
A
Sugiyama
S
S
Ozawa
T
T
Takagi
H
H
D000227:Adenine Nucleotides / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D016572:Cyclosporine / Q000494:pharmacology*; D006503:Hepatic Veins / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000517:prevention & control*
D000227:Adenine Nucleotides; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase