HEPATOCYTE MITOCHONDRION RESPIRATORY CHAIN IN RATS WITH EXPERIMENTAL TOXIC HEPATITIS
A. P. Shiryaeva,1, * E. V. Baydyuk,1 A. V. Arkadieva,1
S. V. Okovityi,2 V. I. Morozov,1 G. A. Sakuta 1
1 Institute of Cytology RAS, St. Petersburg and 2 Department of Pharmacology,
Military Medical Academy, St. Petersburg;
* e-mail: anyasun@mail.ru
The purpose of this study was to examine hepatocyte mitochondrion respiratory chain in rats subjected to ethanol
and CCl4 administration within 4 weeks to induce an experimental hepatitis. Oxygen consumption was
determined as a measure of mitochondrion respiration chain function. The development of liver pathology was
accompanied by fat accumulation, fibrosis, triglycerides and lipid peroxidation increase. Respiratory chain
characteristics damage was found. Endogenous oxygen consumption by hepatocytes isolated from pathological liver was
found 34 % higher compared to control. Exogenous malate and pyruvate substrates delivery didn't stimulate cell
respiration. Rotenone (the inhibitor of the I complex) decreased 27 % oxygen consumption by pathological hepatocytes
while dinitrophenol produced 37 % cell respiration increase. States 3 (V3) and 4
(V4) mitochondrial respiration with malate + glutamate as substrates were found to be 70 and 56 %
higher accordingly compared to control level. V3 and Vd (dinitrophenol
respiration) for mitochondria from pathological liver didn't differ from control when being tested with malate +
glutamate or succinate as substrates. Cytochrome c oxidase activity increased (+ 80 %) as compared to control.
Administration of hypolipidemic agent simvastatin simultaneously with ethanol and CCl4 resulted in
decrease liver fat accumulation, fibrosis and peroxidation products. Simvastatin administration caused hepatocyte
endogenous respiration decrease while malate + pyruvate, dinitrophenol or rotenone delivery produced oxygen
consumption alterations similar to control. However, when isolated mitochondria from liver of simvastatin treated
animals being tested the decrease of oxidative phosphorylation coupling for substrates malate + glutamate was found.
While simvastatin did not cause changes in cytochrome c oxidase activity. We propose the hypothesis that the NCCR
complex in rat mitochondria with experimental toxic hepatitis works extensively on superoxydanion production.
Alterations of SCCR, Coenzyme Q-cytochrome c-reductase, cytochrome c oxidase and ATP-synthase
activities have an adaptive nature to compensate for impaired NCCR function.
Key words: hepatitis, hepatocytes, mitochondrion, respiratory chain, lipid peroxidation, simvastatin
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