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Hepatic monooxygenase activity was studied in rats with various resistance to hypoxia during adaptation to cold. Cold-induced change in the concentrations of cytochromes P-450 and bs and the activity of microsomal metabolism of amidopyrine and aniline were shown to be associated with individual resistance to hypoxia. The content of microsomal cytochromes in highly resistant rats did not change on the fifth day of cold exposure. However, the intensity of metabolic reactions decreased. In low-resistance rats, a cold-induced decrease in the concentration of the cytochromes was not accompanied by significant changes in metabolic rates of amidopyrine and aniline.Key Words: individual resistance to hypoxia; hepatic monooxygenases; cold; adaptation Changes in the functional activities of oxidases in mixed of the liver tractions depend on individual resistance to hypoxia [4]. Cytochrome P-450 is represented by several isoforms with various substrate specificity and immunochemical, catalytic, and spectral characteristics [2].The set of cytochrome P-450 isoforms depends on the species, sex, and age of the animal and particularities of effects of xenobiotics entering the body [3,6]. The intensity and the rate of the synthesis if several cytochrome P-450 isoforms increase during adaptation to cold. The role of cytochrome P450 and its isoenzyme composition in animals with various resistance to hypoxia during adaptation to cold received little attention.Here, we studied the activities of hepatic monooxygenases in rats with various resistance to hypobaric oxygenation under cold exposure. MATERIALS AND METHODSExperiments were performed on male Wistar rats weighing 160-180 g. According to their resistance to hypoxia, the rats were divided into highly resistant (HR)Laboratory of Clinical Problems o[ Ecology, Institute of Regional Patholoqy and Pathomorphology, Siberian Division or the Russian Academy of Medical Sciences, Novosibirsk; Department oI Pharmacology, Novosibirsk Medical Institute and low resistant (LR) groups. One week later, the rats were placed into cold room (0-2~ tor 5 days. Material for investigation was collected on fifth days of the cold procedure and on the third day of the post-cold recovery period. The animals kept at 21~ served as control, the content of microsomal cytochromes was measured [7]. Hydroxylase and demethylase activities of the endoplasmic reticulum enzymes were determined with aniline and amidopyrine substrates [5]. Data were analyzed statistically. RESULTSThe concentrations of cytochromes P-450 and b~ in LR rats were 1.6 and 1.4 times higher, respectively, than those in HR rats. Cold exposure led to various changes in the contents of cytochromes P-450 and b s in hepatic microsomal tractions animals with various resistance to hypoxia. In LR rats, the content of tyrochrome P-450 decreased by 14% (compared with COlatrol) the fifth day of adaptation to cold and did not differ from control on the third day of the post-cold period. The content of cytochrome P-450 in HR rats did not differ significantl...
Hepatic monooxygenase activity was studied in rats with various resistance to hypoxia during adaptation to cold. Cold-induced change in the concentrations of cytochromes P-450 and bs and the activity of microsomal metabolism of amidopyrine and aniline were shown to be associated with individual resistance to hypoxia. The content of microsomal cytochromes in highly resistant rats did not change on the fifth day of cold exposure. However, the intensity of metabolic reactions decreased. In low-resistance rats, a cold-induced decrease in the concentration of the cytochromes was not accompanied by significant changes in metabolic rates of amidopyrine and aniline.Key Words: individual resistance to hypoxia; hepatic monooxygenases; cold; adaptation Changes in the functional activities of oxidases in mixed of the liver tractions depend on individual resistance to hypoxia [4]. Cytochrome P-450 is represented by several isoforms with various substrate specificity and immunochemical, catalytic, and spectral characteristics [2].The set of cytochrome P-450 isoforms depends on the species, sex, and age of the animal and particularities of effects of xenobiotics entering the body [3,6]. The intensity and the rate of the synthesis if several cytochrome P-450 isoforms increase during adaptation to cold. The role of cytochrome P450 and its isoenzyme composition in animals with various resistance to hypoxia during adaptation to cold received little attention.Here, we studied the activities of hepatic monooxygenases in rats with various resistance to hypobaric oxygenation under cold exposure. MATERIALS AND METHODSExperiments were performed on male Wistar rats weighing 160-180 g. According to their resistance to hypoxia, the rats were divided into highly resistant (HR)Laboratory of Clinical Problems o[ Ecology, Institute of Regional Patholoqy and Pathomorphology, Siberian Division or the Russian Academy of Medical Sciences, Novosibirsk; Department oI Pharmacology, Novosibirsk Medical Institute and low resistant (LR) groups. One week later, the rats were placed into cold room (0-2~ tor 5 days. Material for investigation was collected on fifth days of the cold procedure and on the third day of the post-cold recovery period. The animals kept at 21~ served as control, the content of microsomal cytochromes was measured [7]. Hydroxylase and demethylase activities of the endoplasmic reticulum enzymes were determined with aniline and amidopyrine substrates [5]. Data were analyzed statistically. RESULTSThe concentrations of cytochromes P-450 and b~ in LR rats were 1.6 and 1.4 times higher, respectively, than those in HR rats. Cold exposure led to various changes in the contents of cytochromes P-450 and b s in hepatic microsomal tractions animals with various resistance to hypoxia. In LR rats, the content of tyrochrome P-450 decreased by 14% (compared with COlatrol) the fifth day of adaptation to cold and did not differ from control on the third day of the post-cold period. The content of cytochrome P-450 in HR rats did not differ significantl...
Rats with low and high resistance to hypoxia are shown to differ in terms of the baseline activity of liver monooxygenases both in vivo and in vitro. Low-resistance animals are characterized by a significantly higher rate of elimination of antipyrine, hexenal, and nifedipine, as evidenced by shorter half-elimination period and higher urinary concentration of metabolites. The concentration of microsomal cytochromes P-450 and b5 as well as the rates of N-demethylation of amidopyrine, p-hydroxylation of aniline, and hydroxylation of diazepam are considerably higher in rats with low resistance to hypoxia. Key Words: liver monooxygenases, resistance to hypoxia; antipyrine; nifedipine; diazepamRecent investigations show that the mitochondrial respiratory chain provides a molecular basis for considerable species-specific and genetically determined [15] differences in the resistance to hypoxia occurring both at the organism and cellular levels [4]. Previously, we demonstrated opposite changes in the fatty acid composition of the endoplasmic reticulum membranes in hepatocytes from animals with high and low resistance to hypoxia in response to acute hypoxia [9]. However, the activity of the liver oxygen-depended monooxygenase system located in the endoplasmic reticulum in animals with different resistance to oxygen deficiency remains poorly investigated.The aim of the present study was to evaluate in vivo and in vitro the activity of the liver monooxygenase enzyme system in rats differing in individual resistance to oxygen deficiency. MATERIALS AND METHODSExperiments were performed on male Wistar rats weighing 180-220 g. Their resistance to hypoxia was Novosibirsk Medical Institute; Institute of Clinical and Experimental Lymphology, Siberian Division of the Russian Academy of Medial Sciences, Novosibirsk evaluated from the time before the second agonal inspiration during elevation to an "altitude" of 11,500 m at a rate of 50 m/sec in a pressure chamber [8]. Experiments on high-resistance (HR) and low-resistance (LR) animals were carried out 2 weeks after preliminary tests.The in vivo functional activity of liver monooxygenases was assessed by the elimination rate for antipyrine, diazepam, nifedipine, and hexenal. Antipyrine (18 mg/kg) and diazepam (20 mg/kg) were injected intraperitoneally, and nifedipine (5 mg/kg) was administered intragastrally. Blood was drawn from the caudal vein 0.5, 1, 1.5, and 2 h after administration of antipyrine and nifedipine, and 2, 2.5, 3, and 3.5 h after administration of diazepam. The concentrations of the drugs were measured by reverse-phase high-performance liquid chromatography (HPLC) with UV-detection on a Millichrom-lA chromatograph [7]. Elimination of the preparations was calculated by half-elimination time (T,/2) , elimination constant (K,), and clearance (C1) using conventional formulas [7]. The rate of hexenal elimination was evaluated by the duration of hexenal narcosis (100 mg/kg, intraperitoneally) as described elsewhere [2]. The activity of cytochrome P-450 was determined by mea...
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