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The purpose of this study was to assess the protective effects of Naringenin (NG) against cardiotoxicity induced by 5-Fluorouracil (5-FU) in Wistar rats. A total of 48 male rats, all of uniform size were divided into four groups, each consisting of 12 animals. Group 1, designated as the control group, received normal saline (NS) orally (P/O). Group 2 served as the 5-FU toxic group and received intraperitoneal (IP) injections of 5-FU at a dose of 20 mg/kg body weight for the first 5 days. Group 3 received NG orally at a dose of 100 mg/kg body weight per day for 28 days, while Group 4 was injected IP with 5-FU and concurrently received NG orally for 28 days before being sacrificed on the 14th and 28th days of the experiment. The administration of NG significantly reduced the elevated levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor growth factor (TGF-β), while concurrently increasing the levels of interleukin-10 (IL-10). NG also mitigated the heightened Immunohistochemical (IHC) expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and Caspases-3 (Cas-3), while promoting the expression of Nrf2 in the toxic group. In conclusion, the results of this study strongly indicate that NG possesses significant potential for preventing 5-FU-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

5-Fluouracil (FU) is an anti-cancer drug, most commonly used to treat solid malignancies across the globe, and Naringenin (NG) is a natural flavonoid with antioxidant properties. The present study was conducted on rats, which were divided into four groups to estimate the ameliorative effect of NG (100 mg/kg BW/day for 28 days- Group-3) against 5-FU-induced pulmonary toxicity (20 mg/kg BW/day- Group-2 for first 5 days). Group-1 rats were treated with normal saline, whereas group-4 rats were treated with the combination of both NG + 5-FU with same above protocol. During the subsequent period, six rats were sacrificed from each group on the 14th and 28th day of the experiment. Lung tissues were collected for various analyses like antioxidants profile, cytokine profile, histopathology, immunohistochemical and ultrastructure pathology. 5-FU-induced toxicity was characterized by a significant (p<0.05) increase in TBARS in group 2, along with a significant (p<0.05) reduction in GSH and SOD concentration on the 14th and 28th day of the experiment. Whereas, the combination group showed a significant decrease in thiobarbituric acid reactive substrate (TBARS) and increased GSH and SOD levels. Further, a significant (p<0.05) increase in pro-inflammatory cytokines (TNF-α, IL-6, TGF-β and IL-1β) along with a considerable (p<0.05) lower level of IL-10 was observed in group 2 rats and significant improvement in all the parameters were observed in group-4 rats. In addition, on histopathological examination (HP), severe lung damage was observed along with oedema and mild fibrous tissue proliferation were noted which was further supported by scanning electron microscopy. Immunostaining of lung sections revealed strong positivity for NF-κB, COX-2 and TNF-α expressions. However, treatment with NG exhibited a moderate decrease in the intensity of tissue damage observed in group 4 rats compared to group 2 rats. Overall, the intensity of toxicity was more evident on 28th day than 14th day in group 2 rats and a notable improvement in NG treatment of group-4 rats. Based on results, we suggested that NG had protective effects in ameliorating 5-FU-induced pulmonary toxicity. [ABSTRACT FROM AUTHOR]