Under the conditions of hyperthermia, carnosine (~-alanine-L-histidine) normalizes tissue contents of lipid peroxidation products, cytochrome P-450, serotonin, and histamine in rats and increases their survival after extreme hyperthermia. Key Words: hyperthermia; lipid peroxides; biogenic amines; cytochrome P-450; carnosineIt has been suggested that some manifestations of the lipoperoxidation syndrome and changes in the biogenic amine metabolism developing in stress reflect the severity of homeostasis impairments and can be employed to evaluate the effects of various preparations on the resistance of an organism to extreme influences [1,2]. The ability of carnosine to correct lipid peroxidation (LPO) and tissue contents of serotonin and histamine in rats subjected to short-term hypothermia has been recently demonstrated [4]. In the present study we explored the possibility of using this naturally occurring dipeptide to increase the resistance of an organism to hyperthermia. MATERIALS AND METHODSAdult outbred male rats weighing 180-200 g were used. The rats were maintained under standard vivarium conditions and received standard chow. Hyperthermia (40-45~ 1 h) was produced using a ventilated chamber. Rectal temperature was measured with a Term-9 electrothermometer. Camosine (purity >97%) was isolated from bovine muscles and administered per os via gastric tube in a single dose of 250 mg/kg 2.5 h before hyperthermia. The intensity of LPO in blood serum was estimated as described [10]. The content of cytochrome P-450 in liver microsomes was measured by the method [13]. The contents of free histamine [8] and the activity diamino- RESULTSAfter 10 min in thermal chamber (40~ rectal temperature of rats increased from 37.3+0.1 to 40.1+ 0.2~ and practically did not change during 50 rain of the observation period. Under these conditions (1-h hyperthermia, rectal temperature about 40~ for at least 50 rain) the intensity of LPO increased considerably. Serum content of LPO rose during hyperthermia, reached the maximum (almost 7-fold above the norm) 30 min after termination of hyperthermia, and then rapidly decreased (Table 1).A similar dynamics of serum content of LPO products, which points to an LPO "flash" in the body, was observed after other extreme influences, for example, in rats after hypothermia [1,4]. It was hypothesized that LPO products play a dual role in stress: they act as mediators of stress and stress pathology [1]. A decrease in activity of liver cytochrome P-450 system after immobilization, large physical load, and other stressful influences is mediated by LPO products [5,6]. In this study, the activity of liver cytochrome P-450 system was modified by hyperthermia: the cytochrome P-450 content in cytoplasmic reticulum of hepatocytes remained at the level of 65-70% of the norm for at least 60 h (Fig.
We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and beta-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny.
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