Variability of Toxic Action of Carbon Tetrachloride in Rats of Different Ages

Abstract

Age-specific changes define the difference in thresholds of sensitivity to the effect of poison and drug substances. The disclosure of features of mechanisms forming the basis of an observed phenomenon will allow increasing the efficiency of health risks management under the negative influence of chemical factors. The purpose of the study was to identify the hepatotoxic action of carbon tetrachloride in rats of different ages. The Wistar rats of two different age groups -3 and 18 months divided into experiment and control were the objects of the study. The methods of study included clinicodiagnostic analysis of key biochemical indicators: bilirubin, cholesterol, alkaline phosphatase (ALP), ALAT, ASAT, hydroperoxides and malondialdehyde. The obtained results illustrate more expressed toxic xenobiotic impact on the organism of older rats. It was shown by relative (experiment/control) increase of hepatospecific enzymes activity in plasma: ALPyoung = 1.5 times, ALPelderly = 2.4 times, ALATyoung = 5.9 times, ALATelderly = 10.5; ASATyoung 3.5, ASATelderly = 4.9 (the different in other parameters was not so obvious). The regularities revealed during the study contradict literary data on age decrease of activity of human and animal cytochromes ensuring metabolic activation of chemicals, including carbon tetrachloride. Thus, the strengthening of toxic impact of carbon tetrachloride on older animals may be caused by weak hepatic blood flow, reduced oxygenation of tissues and hence, longer contact of hepatocytes with high-reactive metabolites. Keywordsage changes, mechanisms of hepatotoxic action, acute toxic hepatitis.I.