Protective effect of a prostaglandin oligomer on liver mitochondria in situ: time-shared measurements of fluorescence and reflectance in the cold-preserved rat liver

The protective effect of a new oligomeric derivative of prostaglandin B₂, known as OC-5186, was evaluated using time-sharing spectrofluorometry in the coldpreserved rat liver. Experiments were divided into three groups: in group A, a 5000 ng dose of OC-5186 was administered via the peripheral vein, 1000 ng via the portal vein, and 200 ng/ml in University of Wisconsin (UW) solution; in group B, the OC-5186 dosage was ten times greater than that in group A; in group C (control group), liver procurement and storage were performed without OC-5186. At 0, 12, and 24 h after cold preservation at 4°C, the liver was perfused for 30 min at 12°C with oxygenized Krebs-Henseleit solution, after which the perfusate was switched to deoxygenized Krebs-Henseleit solution. Time sharing spectrofluorometry was used to follow NADH fluorescence at 450 nm with a 360-nm excitation wavelength, as well as the reflectance of cytochrome aa₃with 605 minus 620 nm from oxidation to reduction. Rate constants of NADH fluorescence and cytochrome aa₃reflectance were used as indices of integrity of the mitochondrial respiratory chain. In group C, the rate constant of NADH fluorescence decreased significantly (P<0.05) from the control value of 8.31±0.21×10^-3 (sec^-1) to 4.97±0.15×10^-3 and 5.58±0.16×10^-3 (mean±SEM) at 12 and 24 h after cold preservation, respectively. By contrast, in groups A and B, the rate constant of NADH fluorescence was maintained at significantly (P<0.05) higher levels of 6.57±0.54×10^-3 and 7.29±0.48×10^-3, and 6.94±0.44×10^-3 and 6.86±0.44×10^-3 at 12 and 24 h, respectively. The rate constant of cytochrome aa₃reflectance between the OC-5186 groups and the control group was not significant. It is concluded that OC-5186 has a protective effect on the mitochondrial respiratory chain against cold-preservation and/or reperfusion injury.