M. JEEVANALATHAVEMULA SRAVATHI2023-11-032023-11-032022-01-13VEMULA SRAVATHIhttps://krishikosh.egranth.ac.in/handle/1/5810200321The present study was aimed to evaluate protective effect of NARENGENIN (NG) on 5-FLUROURACIL (5-FU) induced cardio-pulmonary toxicity studies in Wistar rats. A total of forty eight (48) adult male abino Wistar rats were divided into 4 groups each. The group 1 (control), group 2 treated with 5-FU (@ 20 mg/kg body weight for 5 days, groups 3 administered with NG (@ 100 mg/kg b.wt) for 28 days and group 4 rats provided with 5-FU (@ 20 mg/kg b. wt +NG (@ 100 mg/kg b. wt). The experiment was carried out for duration of 28 days and each group were sacrificed on 14th and 28th day of experiment. Average b.wts, haematological, biochemical parameters, tissue biochemical or antioxidant profiles, organ morphometry, cytokine profile, gross lesions and ultrastructure (SEM) were assessed. Heart, Lung, liver and kidney samples were collected at the end of the 14th and 28th day of experiment for histopathological and antioxidant profile examination. The 5-FU treated group rats revealed significant (P<0.05) reduction in body weights in comparison to control rats. In group 2 rats, all the haematological parameters were significantly (P<0.05) reduced except TLC. The parameters of organ morphometry in group 2 revealed a significant (P<0.05) increase in the absolute heart and lung weights and significantly (P<0.05) decreased in liver and kidney weights. The thickness of left ventricular wall significantly (P<0.05) increased in group 2 rats. The serum biochemical assays revealed a significant (P<0.05) increase in cardiac biomarkers (LDH, CK-MB, cTn-I and CRP), a significant (P<0.05) increase in lipid profile assay (TG, TC and LDL-c) except HDL-c, significantly (P<0.05) increased (ALT, AST, ALP, BUN and serum creatinine) in all parameters except total protein (TP) and albumin. The tissue biochemical profiles showed a significant (P<0.05) reduction in GSH, SOD concentration and significantly (P<0.05) increased TBARS levels in selective tissues heart, lungs, liver and kidneys of group 2 on 14th and 28th day of experiment. The cytokine activity showed a significant (P<0.05) increase in TNF-α, IL-1β, IL-6 and significant (P<0.05) decrease in IL-10 group 2 rats. Grossly, heart of group 2 rats showed congestion and hypertrophy and lungs showed diffuse haemorrhages and emphysema. Liver and kidney also showed mild to moderate congestion. Microscopically, group 2 rats of heart showed disruption and degeneration of cardiomyocytes, severe interfibrillar haemmorhages oedema and infiltration of MNCs. Lungs shows thickened interstitium, emphysema, focal areas of congestion, red and grey hepatization. Hepato-renal degeneration was also observed in group 2 rats. Ultrastructurally (SEM), group 2 rats showed dilatation and disruption of cardiac muscle fibres with fibrous tissue proliferation with changed morphology of erthrocytes. The cut surface of group 2 rats lung section showed emphysematous alveoli with thin alveolar septa and thickened septa with fibrous tissue proliferation. The changes was mild improved in group 4 rats. In conclusion, the present study suggests that the 5-FU intoxication causes severe cardiac and pulmonary injury, moderate to severe damage in liver and kidneys. Administration of NG moderately reduced the toxic changes induced by 5-FU due to high antioxidant properties.EnglishThesis