SRIVIDYA .G (MAJOR)RAVI KUMAR .PNAVEEN SWAROOP .MSRI HARSHINI VASAMSETTY2024-06-212024-06-212023-03https://krishikosh.egranth.ac.in/handle/1/5810210723Hepatotoxicity is one of the major problem encountered in animals and humans, as the liver is the major target organ for the metabolism of various xenobiotics. Carbon tetrachloride (CCl4) is one of the most commonly used hepatotoxins in experimental studies to investigate liver injury associated with oxidative stress and free radical generation. The use of natural products, without causing much further stress, in preventing and treating liver diseases has gained wide acceptance. Fishes were reported to have higher amounts of essential amino acids, monounsaturated fatty acids, polyunsaturated fatty acids, and minerals. Rastrelliger kanagurta commonly called as Indian mackerel is widely distributed in the tropical Indo-Pacific region and is a rich source of omega-3 PUFAs which significantly regulate cell proliferation, fatty acid metabolism and in reducing inflammation and oxidative stress. Morin a bioflavonoid obtained from members of the Moraceae like Morus alba L (white mulberry), leaves of Psidium guajava, almond and other fruits possess various pharmacological properties such as antioxidant, anti-inflammatory, antineoplastic, antidiabetic, and neuroprotective properties. The major mechanism of hepatic damage produced by CCl4 is lipid peroxidation and oxidative damage by producing free radicals. As the flavonoid and fish extract possess antioxidant activity, they may reduce the hepatotoxicity produced by CCl4. Hence, the present study was designed to evaluate the hepatoprotective effect of Rastrelliger kanagurtha fish extract and morin alone and in combination in CCl4-induced hepatotoxic rats. Thirty Wistar strain male albino rats aged about 45 days were randomly assigned to 5 groups. Group I was maintained as control and received 1% DMSO orally for 3 weeks and olive oil I/P twice a week in the 2nd and 3rd week while groups II, III, IV, and V rats received carbon tetrachloride @ 1ml/kg body weight in olive oil (1:1) I/P twice a week in the 2nd and 3rd week. In addition, Group III & IV rats were administered with R. kanagurtha fish extract and morin at the dose of 300mg/Kg and 30mg/Kg body weight per oral daily for 3 weeks respectively, whereas Group V rats received combination of R. kanagurtha fish extract and morin per oral daily for 3 weeks. Twenty-four hours after the last day of treatment blood samples were collected for the estimation of biochemical parameters and liver samples were collected for gross and histopathological examination. Carbon tetrachloride-induced hepatotoxic rats showed a reduction in body weight, anemia and increase in transaminases. The natural defense mechanism of oxidative damage i.e., reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were reduced and lipid peroxidation marker like TBARS increased significantly when compared to normal rats. Histopathological examination of the liver showed necrotic hepatocytes, ballooning of hepatocytes and centrilobular infiltration of mononuclear cells in sinusoidal spaces were evidenced in the CCl4 treated rats. Treatment with R. kanagurtha fish extract, morin, and their co-administration along with CCl4 led to a reversal in the hepatic biomarkers and a significant reduction in the MDA levels by 67%, 65% and 76% respectively. This trend was in agreement with improved body weight gain, improved antioxidant markers and less severe histoarchitectural changes in the liver. Based on the results it was concluded that the co administration of R. kanagurtha fish extract and morin may have a significant potential and synergistic effect on CCl4-induced hepatotoxicity than their individual treatments.EnglishThesis