Evaluation of tissue-specific effect of neurotoxic agents on metabolic processes in organs of laboratory animals in phase of long-term consequences of severe acute toxic exposure

BACKGROUND: The pathogenesis of the long-term effects of neurotoxic agents remains poorly understood. Tissue specificity, as a qualitative characteristic of the toxic effect, involves selective metabolic process remodeling in specific tissues. AIM: The work aimed to evaluate the tissue specificity of metabolic changes in the long-term effects of acute toxic exposure. METHODS: An experimental study was performed on rats. The toxic agents used were 1.6 mg/kg of phenylcarbamate, 11.5 g/kg of methanol, and 300 mg/kg of lead acetate. The parameters of lipid peroxidation and the antioxidant system were determined using standard biochemical techniques on day 30 after toxic exposure. RESULTS: In the groups of intact animals and those that survived the exposure, lipid peroxidation and the antioxidant system were found to be tissue-specific. The most significant effect, which was common for body tissues, was the shift in diene conjugates, as toxic exposure was followed by a significant decrease in tissue specificity. Regarding the tissue concentration of malondialdehyde, which shows the activity of lipid peroxidation, phenylcarbamate and lead induced an increase in tissue-specific response to toxic effects. This finding showed the selective effect on individual links of oxidative stress in tissues. CONCLUSION: Lipid peroxidation and antioxidant system activity can be considered markers for evaluating the effect of toxic agents on metabolic processes in various tissues. A higher brain tissue sensitivity to the toxic effects can be demonstrated by a higher growth rate of diene conjugates (phenylcarbamate and lead acetate), glucose-6-phosphate dehydrogenase, and superoxide dismutase (methanol). A hepatic tissue-specific response was evidenced by increased activity of glucose-6-phosphate dehydrogenase (phenylcarbamate and methanol) and decreased activity of superoxide dismutase (methanol and lead acetate). The kidneys were particularly susceptible to the impaired utilization of reduced glutathione (methanol) or its formation (lead acetate). The compensatory activation of superoxide dismutase (methanol and lead acetate) was a marker of splenic tissue-specific response.