Cytokine profile in the liver during its diffuse damage and Heptor introduction

Chronic diffuse liver diseases are among urgent problems in the modern world. Exposure to tobacco smoke was used as a model to reproduce liver pathology. The purpose of the study was to evaluate the level of cytokines, i.e., IL-6, IL-18, IL-1α, IFNγ, TNFα, TGF-β1 in an animal model of tobacco intoxication, with administration of Heptor substance for 7, 14, 21 days. The studies were carried out on male rats, divided into intact and 3 experimental groups of 10 rats each. The animals were exposed to tobacco smoke for one, two and four months. For the experiments, a chamber was used with a volume of 0.3 m³ , in which the cigarette smoke was produced. After four months of exposure (3^rd group), Heptor was administered per os at a dose of 120 mg/kg with distilled water for 7, 14, 21 days. After withdrawal from experiment, the liver specimens were sampled, in order to study the level of cytokines. Liver sections were also prepared and stained with Hematoxylin/Eosin. In group 1, inflammatory cell infiltration and degenerative changes were detected in the liver; fibrosis was absent. In the 2^nd group, necrobiotic foci were noted in the liver along with hemorrhages and dystrophic changes; fibrosis was absent. In the 3^rd group, destructive changes, areas of necrosis in the liver, porto-portal and porto-central septa were observed. The level of TNFα was 1.6 times increased in the cytoplasmic fraction of liver tissue in the 1^st group compared to the intact group; in the 2^nd group it was 1.7 times higher; in the 3^rd group it increased by 1.9 times. The concentration of IL-6 was the highest in the group 3. At these terms, TGF-β1 was significantly increased, with destructive changes and liver fibrosis being detected by histology. The use of the drug Heptor for 21 days in animals of the third group contributed to decreased levels of pro-inflammatory cytokines (IL-18, IL-6, IFNγ) in liver tissue, along with reduced TNFα and TGF-β. As a result of their influence, a decrease in the inflammatory response, destructive changes and lower degree of fibrosis was noted, as well as gradual restoration of the liver structures was developed.

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