Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

Abstract

Changes in the redox balance at different levels, which lead to the accumulation of toxic radicals against the background of a decrease in the content of redox-active compounds, i.e., a state of oxidative stress (OS), are considered the leading pathogenetic factor in pathological conditions. Processes of peroxide oxidation of biological substrates, especially cell membrane lipids and lipophilic compounds have both regulatory and pathological effects in the body of animals and humans. For now, it remains relevant to establish the regularities of interaction of metabolism during OS development. Among the large number of existing OS models, attention is drawn to those that can be reproduced in clinical practice, as a complication of treatment measures or an error in the medical strategy, due to a constant influence on peroxidation processes in the body. Important among such means is paracetamol (acetaminophen, APAP) – one of the most common antipyretic and analgesic drugs. In addition to the known hepato-, nephro- and neurotoxic effects of its long-term and/or excessive use, there are data on reproductive toxicity and disorders of lipid metabolism. Therefore, the aim of our work was to determine the lipid profile and the level of sex hormones in male rabbits during paracetamol-induced OS. The study was performed on male rabbits of the Khila breed. According to the principle of analogs, a control group (n = 12) was formed, which were kept on a standard diet, and an experimental group (n = 12), whose animals were simulated the state of OS by oral injection of a solution of paracetamol with food at a dose of 300 mg/kg of weight body once during 21 days. The following results were obtained by determining the dynamics of changes in biochemical indicators in the rabbit body during chronic injection of paracetamol: in the rabbits of the experimental group, after the injection of paracetamol, the level of diene conjugates was 63.0 % higher, and the content of thiobarbiturate-active products was 1.26 times higher (P ˂ 0.05). A decrease in the activity of the antioxidant defence system was also noted – the amount of reduced glutathione decreased by 35.4 %, and the activity of superoxide dismutase decreased by 25.6 % (P ˂ 0.05). The obtained changes were consistent with the comprehensive indicator of total antioxidant activity, which on the 21st day of the experiment was 34.1 % lower than the values of the control group (P ˂ 0.05). At the same time, the level of steroid hormones also changed during the study – the level of total testosterone gradually decreased (on the 21st day – by 22.8 %, and at the end of the experiment – by 30.9 %, P ˂ 0.05), while the level of 17β-estradiol had an upward trend and on the 21st day was higher than the control indicators by 10.7 % (P ˂ 0.05). Significant changes in lipid metabolism were found in male rabbits – the total cholesterol content on the 21st day of the experiment exceeded the data of control animals by 25.3 %, the level of triacylglycerols – by 42.3 %, and the content of low-density lipoprotein cholesterol also increased by 1.1 times (P ˂ 0.05), and the high-density lipoprotein cholesterol level, on the contrary, was reduced by 17.0 % (P ˂ 0.05). In general, the obtained results indicate the relationship between the development of OS with changes in lipid metabolism and the balance of sex hormones, which allows us to use the model of paracetamol-induced OS in rabbits for further research.