CORRECTION OF HISTOLOGICAL CHANGES IN RAT LIVER TISSUE UNDER THE INFLUENCE OF NaNO2 UNDER THE INFLUENCE OF PROVIDIN

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 107 CORRECTION OF HISTOLOGICAL CHANGES IN RAT LIVER TISSUE UNDER THE INFLUENCE OF NaNO2 UNDER THE INFLUENCE OF PROVIDIN M.G’. Soliyeva1, G.T. Abdullayeva2, Z.B. Khosilova3, Q.R. Baratov4, X.J. Beknazarov5, M.J. Toshtemirova6 Base doctoral student, Namangan State University1 Professor department of Biotechnology of the Tashkent State Technical University named after Islam Karimov. Uzbekistan, DSc. Tashkent2 Senior Lecturer, University of Information Technology and management, Karshi, Uzbekistan3 Senior Research Fellow, Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan, PhD, Tashkent4 The scientific center of applied Medicine specializes in neurosurgery in the republic. Pathology manager. Uzbekistan, PhD, Tashkent5 Senior Lecturer department of Biotechnology of the Tashkent State Technical University named after Islam Karimov. Uzbekistan, Tashkent6 https://doi.org/10.5281/zenodo.17674409 Abstract. This article examined the corrective effects of providin substance on histological changes in rat liver tissue caused by NaNO2. In experiments, provodin was found to have a corrective effect on deformational changes in liver tissue and cells caused by NaNO2 exposure, stabilizing liver faoyality. Providin, the thinning of the harmful effects of NaNO2 on liver cells, was scientifically substantiated. The results obtained will give the opportunity to create detoxicant phytopreparations in the future pharmacology based on provodin, which will help to eliminate antidotes or toxic substances from the body. Keywords: NaNO2, liver, tissue, cell, micrascopic taxa, provodine substance, intoxication, detoxicant. Introduction Nitrates, along with their industrial use, have negative effects on the body, are among the global problems of international and national scale [9]. Currently, due to the widespread use of nitrate and nitrite salts in everyday life, production processes, agriculture and the food industry, the process of selling them on online platforms is very fast and the market is quite dynamic [5;4]. However, nitrates and nitrites are described in sources as carcinogens that pose a potential threat to human health. These compounds pose a great threat to human health and the environment, exhibiting toxic, carcinogenic and mutagenic properties [2; 8]. In particular, the continuous use of nitrite salts or an increase in the amount of nitrites prescribed to the body leads to liver physiology and some deformational changes in liver tissue. can lead to several changes in the structure and cause hypoxia in the body [3; 10]. Nitrite consumption in the body, in turn, can have both beneficial and negative effects on the liver. In some cases, scientific literature suggests that nitrite protects the liver from ischemia and reperfusion injury. At the same time, high concentrations of nitrites in the body can cause toxic hepatitis in the liver and affect liver function. The liver plays a crucial role in the processing SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 108 of nitrites, and the degree of effect depends on factors such as the concentration of nitrites, the duration of exposure, and individual sensitivity [1; 7]. In modern medicine and pharmacology, plants are widely used to prevent various degrees of poisoning of the body by various toxicants (chemical reagents, xenabiotics, pesticides, and nitrites) and nitrites. Plants have the ability to protect cells and tissues from the harmful effects of toxic substances, including heavy metals, organic xenobiotics, nitrites, and detoxify them [10; 4; 6]. In this regard, the scientific work on the analysis of histological changes in rat liver tissues under the influence of NaNO2 and the correction of the identified disorders under the influence of plant substances is of significant scientific and practical importance. Purpose of the research To analyze the histological changes in rat liver tissues under the influence of NaNO2 and the correction of the identified disorders under the influence of providin. Research methods and materials Scientific research was conducted in collaboration with employees of Namangan State University and the Institute of Bioorganic Chemistry of the Academy of Sciences of the Republic of Uzbekistan. The experiments were conducted in vivo. For the experiments, outbred laboratory rats weighing 180-220 g were selected. The feeding of laboratory animals was carried out in standard rational vivarium conditions. For the experiments, laboratory animals were divided into IV groups and the groups were formed as follows: group I - healthy control (physiological solution), group II - intoxication experimental group (NaNO2), group III - treatment experimental group ((NaNO2) + sodium sulfate + ascorbic acid), group IV - correction experimental group ((NaNO2) + sodium sulfate + ascorbic acid + providin). The number of rats in each group is 5. The repetition of the experiments is n = 4-6. The duration of the experiments is 15 days. When conducting the experiments, a dose of 20 mg / kg of NaNO2 was selected in the animals. Obtained results and their analysis It is known that the liver, in addition to homeostatic control of the amount of substances entering the blood with food, is also involved in the neutralization of toxic substances entering the body (ammonia, intestinal decay products, bilirubin, etc.). The liver is a very sensitive organ to the effects of toxic substances, especially nitrites. Nitrite entering the body can cause various changes in liver tissue, including impaired protein synthesis, replacement of healthy tissues with scar tissue (cirrhosis), and fatty infiltration. Chronic exposure to nitrates disrupts protein synthesis in the liver and leads to a change in its qualitative composition. Diffusional changes in the liver under the influence of nitrites, i.e., a deviation of the tissue structure from the normal state, lead to the process of fatty infiltration in the liver. This process can be a contributing factor in the development of liver diseases caused by nitrites directly in the liver. Chronic liver damage by nitrites is observed in liver tissue, and the liver is unable to fully perform its physiological function. In our studies, scientific results were obtained in accordance with the above-mentioned explanations. In our studies, when we studied the liver tissue of the healthy control group (physiological solution) based on microscopic examinations, it can be seen that this group retained the classic liver lobe structure, hepatocytes were arranged radially around the central vein, and the portal triads (hepatic hepatocytes, arterial network, portal vein network, and bile ducts) were clearly distinguished anatomically (Fig. 1-A). The morphological and histoarchitectural structure of this group of liver tissues was preserved in a normal state. In the liver of representatives of this group, we can see that each functional zone was clearly delimited, and structural units were distinguished. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 109 Figure 1. Microscopic appearance of liver tissue of control group I rats. Note: Figure A (Stain hematoxylin eosin. X-100); Figure V (Stain hematoxylin eosin. X400). In particular, it is clearly seen that hepatocytes in the periportal area are arranged correctly and compactly, and their cytoplasm has strong eosinophilic staining. The nuclei are oval or round in shape, hyperchromic and centrally located. In the middle lobular area, hepatocytes showed reduced cytoplasmic eosinophilia, and some cells showed binucleated hepatocytes, which is considered a morphological feature characteristic of regenerative activity (Fig. 1-B). Although certain structural changes were observed, the general tissue structure was preserved. Pathomorphological changes were clearly expressed in the centrolobular area: granular dystrophy, pericellular edema, and nuclear hypochromia or anucleated hepatocytes were observed in the cytoplasm of hepatocytes. The number of Kupffer cells increased significantly, indicating increased phagocytic activity in the liver. It is possible that changes in this zone are associated with hypoxia processes. Figure A Hematoxylin eosin stain. X-100 Figure B Hematoxylin eosin stain. X-400 Figure 2. II-intoxication (NaNO2) experimental group-micrascopic coring of rat liver tissue. Figure A Hematoxylin eosin stain. X-100 Figure B Hematoxylin eosin stain. X-400 SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 110 Note: Figure A (Stain hematoxylin eosin. X-100); Figure B (Stain hematoxylin eosin. X400). In general, the zonal differentiation of liver tissue in our animals of group I and the control healthy (physiological solution) group fully correspond to the principles of the Rappaport model. When analyzing the morphofunctional state of the tissue within the lobules and acini, it was found that the periportal zone had a well-preserved trophic supply, while the centrilobular zone had a high sensitivity to hypoxic-ischemic changes. This is important in assessing the local reactivity of the liver to pathological processes and its morphological adaptation capabilities. The experiments continued with the study of microscopic changes in the liver tissues of animals of the experimental group of intoxication (NaNO2) of group II (Fig. 2). Also, during the experiments, by treating animals affected by (NaNO2) (group III treatment experimental group ((NaNO2) + sodium sulfate + ascorbic acid), their liver tissues were microscopically examined (Figure 3). Figure A Hematoxylin eosin stain. X-100 Figure B Hematoxylin eosin stain. X-400 Figure 3. Microscopic appearance of liver tissue of rats of the experimental group of treatment group III. Note: Figure A (Stain hematoxylin eosin. X-100); Figure B (Stain hematoxylin eosin. X400). In the representatives of the treatment group III, it was found that the liver tissue - the cytoplasm of hepatocytes was homogeneous and uniformly stained. The nuclei were located in the central part of the cell, clear, euchromatic, without signs of pyknosis and karyorrhexis (Figure 3A). Mitotic phases and regenerative symptoms were visible in some cells. There were hyaline bundles and a decrease in phagocytosis in the cytoplasm, a small amount of centrilobular edema and necrosis (Figure 3B), inflammatory infiltrates in the portal tracts decreased; the number of lymphocytes and neutrophils approached the physiological norm. Kupffer cells were active and preserved in shape, the endothelial cells of the sinusoids were intact, and the nuclei were clear and symmetrical. These data show that the selected sources for the treatment of the liver in animals poisoned with NaNO2 (sodium sulfate + ascorbic acid) had an effective effect and led to changes in the morpho/physiological parameters of the liver. At the end of the experiments, correction studies were conducted in animals poisoned by NaNO2, in addition to treatment, by administering providin, and representatives of this group were designated as group IV correction experiment (NaNO2) + sodium sulfate + ascorbic acid + providin). SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 111 Figure А Hematoxylin eosin stain. X-100 Figure B Hematoxylin eosin stain. X-400 Figure 4. Microscopic appearance of liver tissue of rats in the IV-correction experimental group. Note: Figure A (Hematoxylin eosin stain. X-100); Figure B (Hematoxylin eosin stain. X-400). As a correction, the liver of our group of studied representatives showed homogenization in the cytoplasm of hepatocytes and a decrease in the number of vacuoles, the intensity in the nucleus was euchromatin type, in some places signs of pyknosis and karyolysis were detected, in some cells hepatocytes were detected in the mitotic phase, the foci of necrosis around the central veins were visible with a reduced volume or with a limited extent (Fig. 4-B). Lymphoid infiltrates in the portal tract decreased, signs of slight edema in the sinusoidal space, there was intensity in the cytoplasm of endothelial cells (Fig. 4-A), stasis and microhemorrhages were detected in small quantities in and around the microvascular space. The number of fibrous cells in the periportal areas decreased. The number of Kupffer cells around the central vein significantly increased. The above experiments show that 20 mg/kg of NaNO2 had a detrimental effect on the liver tissue of the experimental group of animals. These changes were expressed in the presence of signs of vacuolar and granular dystrophy in the liver, the occurrence of focal necrosis foci around the veins, the loss of cellular structure of hepatocytes, the detection of inflammatory infiltrates and fibrosis (growth of collagen tissue) in the liver. Providin reduced the harmful effect of NaNO2 on liver tissue and exerted a corrective effect on liver cells. Under the influence of providin, the size of the necrotic foci around the central veins of the liver disappeared, lymphoid infiltrates in the portal tract decreased. The number of fibrous cells in the periportal areas decreased. The number of Kupffer cells around the central vein was significantly increased. Conclusion: Thus, providin inhibited the harmful effect of NaNO2 on liver cells and exerted a corrective effect on liver tissue. 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