The aim of the study was to comprehensively assess histological parameters of the hypothalamic neurosecretory and immune systems in pregnant rats exposed to passive smoking and their offspring.Material and methods. We studied morphological and immunological parameters of pregnant Wistar rats exposed to passive smoking and those of the control group, as well as their offspring. The obtained material was processed using histological, immunohistochemical, morphometric and immunological methods.Results. The results obtained demonstrated that in rats exposed to passive smoking, the sizes of neurosecretory cells (NSCs) of the supraoptic (SO) and paraventricular (PV) nuclei of the hypothalamus increased, the number of p53 positive NSCs increased, and bcl-2 protein expression decreased. Tobacco smoking caused formation of a proaptotic dominant in the neurosecretory cells of the supraoptic and paraventricular nuclei of the hypothalamus. Passive smoking led to a decreased body weight, a decreased number of thymocytes and myelokaryocytes in pregnant rats. In young rats born from the animals exposed to passive smoking, there was a slowdown in the processes of postnatal differentiation of the adrenal cortex (fascicular zone) with preservation of the extended zone of the fetal cortex. Notably, histo- and morphogenesis both in the organs of the primary (thymus) and secondary (spleen, lymph nodes) links of immunogenesis were delayed. In such young rats, a decreased body weight, thymus, number of thymocytes and splenocytes were recorded.Conclusion. Total results of the study evidence that passive smoking causes immunosuppressive changes in pregnant rats and their offspring combined with delayed postnatal histogenesis and proapoptotic manifestations in the nonapeptide-dergic hypothalamicpituitary adrenocortical system, which can be regarded as an unfavorable factor in the implementation of the neuroendocrine regulative mechanisms of adaptogenesis processes.
Currently, experimental studies are actively conducted to assess the effects of low-molecular-weight polypeptide mediators on the immune system, in order to design new immunomodulatory drugs. However, the specific effects of individual peptides on the immune system of experimental animals and their offspring remains insufficiently studied, thus requiring relevant research in this aspect. Our study evaluated the effect of the peptide homologue of the of adrenocorticotropic hormone fragment (15-18) (laboratory code, KК1) on immunological parameters of pregnant rats and their offspring using experimental models of passive maternal smoking exposure. The immunological parameters were studied in 96 pregnant Wistar rats weighing 200-300 g, exposed to passive tobacco smoking and receiving a synthetic peptide KK1, which is a structural analogue of the ACTH15-18 sequence fragment (Acetyl-(D-Lys)-Lys-Arg-Arg-amide), as well as probable effect on their offspring tested on the 14th day after birth (76 rats). Experimental rats were fumigated with tobacco smoke for 8 hours daily from the 1st to the 20th day of pregnancy. Synthetic peptide KK1 was administered to pregnant rats in the form of an aqueous solution at a dose of 40 mcg / kg / day five times a day for 10 days. Weights of whole body, thymus and spleen were determined in all animals, the number of leukocytes, thymocytes, splenocytes, myelocaryocytes, circulating immune complexes were assessed in accordance with common protocols for experimental laboratory animals. The data were analyzed by MannWhitney U test. The significance level was set at p 0.05. Administration of the KK1 peptide to both control and experimental pregnant rats was accompanied by multidirectional changes in the number of cells in lymphoid organs. The positive trend of shifts in immunological parameters when exposed to the peptide KK1 seems to be based on the possible reduction of the consequences of the toxic effect of tobacco smoke due to the anti-inflammatory effect of this drug, as well as its ability to limit the development of free radical reactions. It is shown that the studied peptide contributes to the positive dynamics of multiple immunological parameters in experimental animals subjected to passive smoking. Further studies are required to assess the mechanisms of immunotropic action of the ACTH15-18 peptide homologue.
The literature covers multiple negative effects of active and passive tobacco smoking upon the human body and experimental animals. Much lesser attention is given to the features of the immune system in offspring from the passively smoking experimental animals. In previous works, we studied physiological and immunological parameters in the infant rats born from passively smoking rats. The present work expands the scope of this direction and is devoted to assessment of immunological parameters in passively smoking pregnant rats and their offspring. Quantitative determination of immunological parameters was carried out in pregnant Wistar rats exposed to passive tobacco smoking and in 65 pup rats from smoke-exposed and nonexposed animals. The experimental rats were exposed to tobacco smoke for 8 hours from the 1st to the 20th day of pregnancy. In all animals, the body weight, thymus and spleen, the number of white blood cells, thymocytes, splenocytes, and myelocaryocytes were determined. On the 20th day of pregnancy, the smoking rats showed a significant decrease in the weight of animals, the number of thymocytes and myelocaryocytes. A decreased body mass of animals and their thymus glands, lower number of thymocytes were registered in pup rats born from smoking females as compared with control animals. These changes in immunological parameters may be based on a number of possible reasons. On the one hand, tobacco smoke promotes activation of free-radical processes with a simultaneously decreased efficiency of antioxidant mechanisms. This activation may result from exposure to the components of tobacco smoke, in particular, chromium, as a metal of variable valence, as well as benzene, which is transformed by the free-radical oxidation mechanisms. On the other hand, some tobacco smoke components may promote apoptosis which plays a significant role in the cellular exhaustion of immunogenesis system. Moreover, a decreased number of thymocytes may be caused by their migration from cortical areas to the medulla, followed by release into bloodstream. Thus, the results obtained indicate that the detected changes in these parameters are more pronounced in pregnant rats who were exposed to tobacco smoke and their offspring, and expand the knowledge of changes in the immune system in the offspring of passively smoking animals. The presented data may present a basis for development of drugs that reduce toxic effect of ecotoxicants, including passive tobacco smoking.
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