Analysis of factors influencing apoptotic processes during formation of long-term health effects of severe acute poisoning with neurotropic toxicants

Background . The nervous system damage caused by neurotoxicants is characterized by various morphological changes, manifested mainly by dystrophic and necrotic processes. The key mechanisms of post-intoxication asthenia pathogenesis, determined by the specifics of the toxicant, involve activation of apoptosis, trophic disorder, lipid peroxidation (LPO), neuropeptide regulatory insufficiency, as well as cerebrospinal fluid dynamics disorders. Objective. Quantification of the contribution of apoptosis, oxidative stress, and neurotrophin regulation processes to the formation of long-term health consequences of severe acute poisoning with neurotropic toxicants. Material and methods . Experimental studies were performed in male rats. The following toxicants were used: phenylcarbamate (1.6 mg/kg bw), methanol (11.5 g/kg bw), lead acetate (300 mg/kg bw). The period of formation of long-term health effects was 30 days. The level of apoptosis of the brain temporal cortex neurons was evaluated by the TUNEL method. The identification of blood plasma neurospecific proteins was carried out by the ELISA method. Evaluation of LPO and antioxidant system was carried out by standard biochemical methods. Results . Exposure to the substances caused the signs of toxic effects in rats on days 1–2. The maximum severity of poisoning with phenylcarbamate was on the first day, while the maximum severity of poisoning with methanol and lead acetate was manifested on the second day. By days 5–7, the survived animals showed a normalization in the status regardless of the toxicant. On day 30, violations were detected, the totality of which allowed the survived animals to be divided into subgroups according to the manifestation of functional signs of long-term health effects of acute poisoning. Conclusions. The formation of long-term health effects of severe acute poisoning with the studied neurotoxicants was shown to be associated with an increase in the number of TUNEL positive neurons and a decrease in the S100 protein serum concentration. Lipid peroxidation in brain tissues during the specified period did not play a significant role in apoptosis activation.