Glucural (amigluracyl) improves survival of isolated rat hepatocytes in suspension.

Nonsteroid anti-inflammatory drug glucural (water-soluble N-methyl-D-glucosamine complex with 6-methyluracyl) improves survival of isolated rat hepatocytes stored in suspension. This effect of glucural is presumably explained by its membranotropism.

Superoxide anion production by the mitochondrial respiratory chain of hepatocytes of rats with experimental toxic hepatitis.

The progression of toxic hepatitis is accompanied by the activation of oxidative processes in the liver associated with an enhancement of the mitochondrial respiratory chain activity and superoxide anion production (O(2)(*-)). The purpose of this study was to examine our previously formulated assumption concerning the predominant contribution of the complex I to O(2)(*-) production increase by the mitochondrial respiratory chain of hepatocytes in toxic hepatitis (Shiryaeva et al. Tsitologiia, 49, 125-132 2007). Toxic hepatitis was induced by a combined application of CCl(4) and ethanol. Respiratory chain function analysis was executed with submitochondrial particles (SP) in the presence of specific inhibitors. It was shown that the rate of O(2)(*-) production by SP of animals with toxic hepatitis, when NADH was delivered, was 2.5-fold higher as compared with the control. The rates of O(2)(*-) production by SP of rats with toxic hepatitis in the presence of NADH or NADH+ rotenone were similar. The O(2)(*-) production rate by control SP in the presence of NADH + rotenone corresponded to the O(2)(*-) production rate by toxic hepatitis SP when only NADH was delivered. When NADH+ myxothiazol were delivered to the incubation system, O(2)(*-) production by toxic hepatitis SP was 72% higher than for the control. Conversely, in the presence of antimycin A, the production of O(2)(*-) by toxic hepatitis SP was lower compared to the control. Collectively, the presented data indicate that the O(2)(*-) production rate was enhanced by the complex I of the hepatocyte mitochondrial respiratory chain in experimental toxic hepatitis. Complex III contribution to the production of O(2)(*-) was insignificant. We assume that the increase in O(2)(*-) production by the respiratory chain may be considered not only as the mechanism of pathology progression, but also as a compensatory mechanism preserving the electron transport function of the mitochondrial respiratory chain when complex I functioning is blocked in part.

Hepatocyte mitochondrion electron-transport chain alterations in CCl(4) and alcohol induced hepatitis in rats and their correction with simvastatin.

The goal of this study was to examine the state of hepatocyte mitochondrial respiratory chain of rats with toxic hepatitis induced by CCl(4) and ethanol. Oxygen consumption by hepatocytes and mitochondria was determined. Endogenous oxygen consumption by pathological hepatocytes was 1.3-fold higher compared with control. Rotenone resulted in 27% suppression of respiration by pathological hepatocytes whereas 2,4-dinitrophenol produced a 1.4-fold increase of respiration. States 3 and 4 of mitochondrial respiration with malate and glutamate were found to be higher as compared to control. State dinitrophenol and state 3 respirations were similar within every group of animals when being tested with malate and glutamate or succinate. Cytochrome c oxidase activity in hepatitis was 1.8-fold higher compared with control. Simvastatin administration resulted in a decrease in hepatocyte endogenous respiration in hepatitis. The presented data lead to the assumption that the increased oxygen consumption by the respiratory chain of pathological mitochondria to be linked mainly with the altered function of complex I.