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.
Shiryaeva
A
A
Laboratory of Cell Pathology, Institute of Cytology RAS, St. Petersburg, Russia. anyasun@mail.ru
Baidyuk
E
E
Arkadieva
A
A
Okovityy
S
S
Morozov
V
V
Sakuta
G
G
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy / Q000201:enzymology*; D002492:Central Nervous System Depressants / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity; D006519:Hepatitis, Alcoholic / Q000188:drug therapy / Q000201:enzymology*; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D002492:Central Nervous System Depressants; D000431:Ethanol; D019821:Simvastatin; D002251:Carbon Tetrachloride; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I