Evaluation of cytoprotective drugs for liver preservation by pyridine nucleotide fluorometry.
The cytoprotective effects of membrane-stabilizing drugs, such as chlorpromazine, allopurinol, dibucaine, phenoxybenzamine, and OP41483 (prostacyclin analogue), administered to perfusate and preservation medium were studied in rat liver, after 24 hours' preservation, by assessment of pyridine nucleotide fluorescence. On the fluorometric trace curve, amplitude (RxA) and velocity (RxV) from oxidation to reduction were determined. Percent decrease of RxA (%RxA) and that of RxV (%RxV) after 24 hours' preservation were calculated. At the end of preservation, the concentration of total adenine nucleotides of the liver, hepatic adenylate energy charge, and prepared mitochondrial oxidative phosphorylative activity were also measured. In the groups given phenoxybenzamine, dibucaine, and allopurinol, there was no significant difference among these parameters. In the chlorpromazine group, energy charge and %RxV were higher than in the drug-free group (p less than 0.05). In the OP41483 group, both energy charge and phosphorylation rate were significantly higher (p less than 0.05) and %RxV was significantly high (p less than 0.01) at concentrations of more than 3 nmol/L, compared with the values for those without drugs. These results suggest that the Redoximeter can provide accurate information on the effectiveness of cytoprotective drugs. It is also suggested that OP41483 has potential application for maintaining graft viability for human liver transplantation.
Ozaki
N
N
Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Tokunage
Y
Y
Wakashiro
S
S
Ikai
I
I
Morimoto
T
T
Shimahara
Y
Y
Kamiyama
Y
Y
Yamaoka
Y
Y
Ozawa
K
K
Nakase
Y
Y
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D009926:Organ Preservation; D010084:Oxidation-Reduction; D010643:Phenoxybenzamine / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011742:Pyrimidine Nucleotides; D051381:Rats; D011919:Rats, Inbred Strains
D011465:Prostaglandins, Synthetic; D011742:Pyrimidine Nucleotides; D010643:Phenoxybenzamine; D000493:Allopurinol; D011464:Epoprostenol; D003992:Dibucaine; C035847:ataprost; D002746:Chlorpromazine