CONCENTRATIONS OF MITOCHONDRIAL AND MICROSOMAL CYTOCHROMES IN LIVER TISSUE IN EXPERIMENTAL DRUG-INDUCED FATTY DEGENERATION OF THE LIVER T. N. Makarenko, A. M. Dudchenko, and L. D. Luk'yanova UDC 612.351.11.015:616.36-003.826-021].001.6 KEY WORDS: fatty degeneration of the liver; mitochondrial and microsomal cytochromes; resistance to hypoxia Fatty degeneration of the liver is a disease with multiple etiology. The causes of this pathological state include not only diabetes, general obesity, and overindulgence in alcohol, but also various xenobiotics and drugs, including the tetracyclines. The mechanism of action of the tetracycline antibiotics has been the subject of much research, and the principal causes of hepatotoxicity are considered to be metabolic processes such as protein synthesis [1], aerobic respiration and oxidative phosphorylation [14], hormonal regulation of fat and carbohydrate metabolism [13], and activation of lipid peroxidation [4]. However, the specificity of the triggering mechanisms leading to the development of fatty degeneration remains unknown. Research on isolated hepatocytes and mitochondria has revealed disturbances of mitochondrial oxidation of fatty acids [9] and of synthesis of mitochondrial apoproteins, which are responsible for the elimination of triglycerides from the liver [12]. A special role of the microsomal oxidation system in the patho- genesis of toxic hepatitis has been established [6]. The aim of this investigation was to assess the state of the systems of mitochondrial and microsomal oxida- tion in a tetracycline model of fatty degeneration of the liver. The existence of animals differing in individual sensitiv- ity to hypoxia, which may play a role of pathogenetic factor in the development of fatty degeneration of the liver, determined the choice of rats with low and high resistance to hypoxia as the test object. EXPERIMENTAL METHOD Experiments were carried out on noninbred male rats (180-220 g), kept on the standard animal house diet. Fatty degeneration of the liver was induced with tetracycline hydrochloride (TC), which was administered in a dose of 500 mg/kg in 1% starch mucilage by the intragastric route daily for 5 days. Control animals received 1% starch mucilage alone under the same conditions [3]. The rats were divided initially on the basis of their resistance to hypobaric hypoxia, into those with low (LR) and high (HR) resistance [11]. The reaction of the animals to acute hypoxia was assessed by the method generally adopted in the writers' laboratory [7]. The liver of the animals, anesthetized with ether, was perfused with physiological saline, after which a homogenate was prepared in Hanks' solution with glucose. Alanine aminotransferase (ALAT) activity [8], the cytochrome P-450 tevel [10], and the content of mitochon- drial cytochromes b, c +, c 1, and a [2] were determined in the liver homogenate. The total lipid content in the liver homogenate was determined with the aid of standard kits ("Lachema," Czechoslovakia). Laboratory of Bioenergetics, Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow (Presented by Academician of the Russian Academy of Medical Sciences L. D. Luk'yanov.). Translated from Byulleten' t~ksperimental'noi Biologii i Meditsiny, Vol. 114, No. 12, pp. 584-585, December, 1992. Original article submitted April 9, 1992. 0007-4888/92/0012-1765512.50 9 Plenum Publishing Corporation 1765