The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.

. The aim of this study was to evaluate the effects of quercetin (QC) and its complex with 2-hydroxypropyl-β-cyclodextrin (QECD) in healing burn related skin wounds in the rat model. Male Wistar rats were subjected to third-degree burn injury of skin in the interscapular area using a metal rod heated to 80 °C. The area of the skin which the burn was applied to was secured from the surroundings by the protective chamber. In order to estimate the efficacy of different treatment modalities the experiments were carried out in two stages. On first stage of the study, the group of animals (n = 21) was subjected to burn injury and the wound surface was not affected with additional procedures except the substances for treatment being applied. During the second stage of the study with another group of animals (n = 18) the removal of necrotic tissue was carried out over the period of 3 to 7 days. The progress of the wound healing was followed by performing morphometric analyses in order to determine complete re-epithelialization. The phagocytic index of neutrophils was determined in washouts from the wounds during the healing process. The animals used on the first stage of the study were sacrificed at day 21 of the experiment and those on the second stage at day 43 and the tissues were subjected to histological examination. The amounts of white blood cells and phagocytic index of neutrophils were calculated in blood samples followed by the measurements of metabolic activities of neutrophils. The removal of necrotic tissue has been found to promote better wound healing caused by thermal exposure. No reliable evidence has been obtained on QC or QECD abilities to significantly accelerate the burn wound epithelialization. The square of the secondary wound scab covered the damaged skin surface has been found to be decreased in the first group of animals on the 14th day followed by the exposure while the rate of wound epithelialization has been found to be increased in the second group of animals at the final stage of wound healing under the treatment with substances being investigated. As a result the ability of QE and QECD to normalize the white blood cell differential, phagocytic and metabolic activities of neutrophils recruited to a wound and neutrophil blood levels has been found.

Macroscopic, histological, electron microscopic, microbiological, and immunological methods were used to study the healing of full-thickness skin wounds in laboratory rats under the influence of quercetin and its complex with 2-hydroxypropyl-β-cyclodextrin. It was revealed that under the influence of quercetin, the wound was completely covered with the epidermis almost a day earlier than in the control, and under the influence of a complex with 2-hydroxypropylβ-cyclodextrin 2.2 days earlier (p < 0.02). This was mainly due to the acceleration of marginal epidermization. There was no positive effect on the wound contraction. Quercetin and especially its complex with cyclodextrin had a stimulating effect on the phagocytic and metabolic activity of neutrophils both on the wound surface and in the blood of animals. The bacterial microflora present on the wound surface during healing coincided with the microflora of the intact skin. Neither the quercetin, nor the quercetin-2-hydroxypropyl-β-cyclodextrin significantly affected its composition.

A model was developed, on the basis of which the features of healing of a full-thickness skin wound were studied in laboratory rats using macro-, micro- and ultramicroscopic methods. It was found that during this process, two borders are formed on the surface of the wound ‒ one on the edge of the dermis and the second on the edge of the epidermis. It is shown that a granulation tissue can be formed not only due to the restructuring of fibrin, but also due to the reorganization of a subcutaneous tissue. It is hypothesized that the wound contraction occurs not only due to the contraction of collagen fibrils by myofibroblasts, but also due to the retraction of collagen fibers in the cytoplasm of these cells. Attention is drawn to the restoration of the elastic layer as an essential component of the skin regenerate. The reasons for the appearance of a longitudinal elongated shape and orientation along the sagittal line of the scar, which remains for life at the site of the former skin damage, are explained.

A method for revealing genetic affinity between laboratory rats has been developed, which is based on the transplantation of ear skin-chondrocyte allografts onto the surface of a full-thickness skin defect. On the example of Wistar rats (laboratory rats were taken from three research institutes), it was shown that the rejection of allografts occurs in the interval between 8 and 21 days with the same genetic differences that existed between the animals. However, at the same time, only those structures of ear allografts such as the dermis, epidermis and its derivatives die and are rejected, but the layers of chondrocytes are submerged under the granulation tissue and remain in a viable position for at least 210 days. The latter phenomenon is probably due to the membranes that cover the chondrocytes and act as an immunological barrier.