RESUMEN
The article solves a current task concerning a substantiated use of acetylation phenotype as susceptibility biomarker to unfavourable effect of chemical substances in scientific studies. Objective: to study a combined effect of sodium nitrate and cadmium chloride on the prooxidant-antioxidant balance of the blood, liver and functional state of the central nervous system in young rats with different acetylation type. The experimental studies were performed on immature male rats 1,5-month of age. The experimental animals were divided into two groups according to the amount of general sulfadimine excreted with urine: "rapid" and "slow" acetylators. 2 subgroups were differentiated in every group: I - control animals, II - animals subjected to administration of cadmium chloride and sodium nitrate. Administration of sodium nitrate and cadmium chloride to animals in the doses 1/15 DL50 and 1/150 DL50 respectively during 14 days found that at the young age "slow" acetylation type is susceptibility marker, and the criteria of a harmful effect in them are the following: 25% increase protein peroxide oxidation in the blood plasma, 34% and 30% increase of average molecular peptides and ceruloplasmin respectively, and 6,7 times increase of methemoglobin (hemiglobin) concentration. Nitrate-cadmium intoxication caused inhibition of the integral behavioural activity both in slow and rapid acetylators. Disturbed behavioural activity in young animals with "slow" acetylation type under conditions of subacute effect of sodium nitrate and cadmium chloride is caused mainly by an increased content of liver lipoperoxidation secondary products and less - by the levels of average molecular peptides and ceruloplasmin in the blood plasma, and in "rapid" acetylators - by increased products of oxidation-modification proteins.
Asunto(s)
Acetilación/efectos de los fármacos , Cadmio/toxicidad , Nitratos/toxicidad , Animales , Biomarcadores/metabolismo , Intoxicación por Cadmio/metabolismo , Masculino , Fenotipo , RatasRESUMEN
Objective of the work is to study enalapril effect, a blocker of renin-angiotensin system, on glutathione chain of the antioxidant system of the cerebral cortex and hippocampus of rats with experimental neurodegeneration. The experiments were conducted on nonlinear laboratory albino male rats with their body weight of 0,18-0,20 kg. The model of neurodegeneration was created by means of intraperitoneally administration of scopolamine hydrochloride (Sigma, USA) during 27 days in the dose of 1 mg/kg. Since the 28th day of the experiment enalapril (Zdorovye, Ukraine) was introduced intraperitoneally in the dose of 1 mg/kg in 1 ml of physiological solution once a day during 14 days. The content of reduced glutathione in male rats with scopolamine-induced neurodegeneration after introduction of enalapril increased in the cerebral cortex 1,8 times as much, and in the hippocampus - 1,2 times. Under enalapril effect the content of sulfhydryl groups increased in the cerebral cortex and hippocampus 1,3 and 1,1 times respectively. A positive effect of enalapril was characterized by an increased activity of glutathione reductase in the cerebral cortex 1,7 times as much, and 1,6 times - in the hippocampus. Thus, enalapril improves the indices of glutathione chain of the antioxidant system of the cerebral cortex and hippocampus, which is indicative of its neuroprotective ability under conditions of scopolamine-induced damage and development of neurodegenerative processes in rats.
Asunto(s)
Antioxidantes/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Enalapril/farmacología , Glutatión/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/prevención & control , Fármacos Neuroprotectores/farmacología , Animales , Humanos , Masculino , Enfermedades Neurodegenerativas/inducido químicamente , Ratas Wistar , EscopolaminaRESUMEN
The experiments conducted on non-linear mature laboratory albino rats determined that under conditions of subacute cadmium-nitrate intoxication the indices of proteinuria and acid-regulating renal function depend on acetylation phenotype. Unlike rapid acetylators considerable increase of protein concentration in urine (192,8%, Ñ<0,05) and standardized by glomerular filtration protein excretion (141,7%, Ñ<0,05) are indicative of higher susceptibility of rats with slow acetylation type to nephrotoxic action of cadmium chloride and sodium nitrate. Lack of protein loss with urine and adaptive-compensative character of acid-regulating renal function changes directed to elimination of hydrogen ions excess from the body give evidence concerning less intensive damage of the nephron tubular portion in rats with rapid acetylation type, and at the same time do not exclude development of nephropathy. In order to confirm the significance of acetylation phenotype for assessment of susceptibility and degree of cadmium-nitrate damage of the kidneys the condition of other renal functions should be examined with analysis of biochemical criteria of nephrotoxicity, which is of an important practical value for the selection of appropriate pharmacotherapy.