| Summary: | Background: Ethanol intake can cause oxidative stress, tissue inflammation, and renal damage by producing free radicals. Flavonoids are phenolic chemicals found in a range of fruits, vegetables, tea, and wine. More significantly, many flavonoids are active constituents in traditional Chinese herbal medicines, which have no adverse effects in general. However, there is a paucity of research on the therapeutic effectiveness of Citrullus lanatus seed flavonoids against renal damage. Method: The rats were split into six groups: normal, ethanol (10 ml/kg of 50% ethanol), flavonoids (100 mg/kg/day), ethanol plus low and high flavonoid dosages (ET + 100 and 200 mg/kg FCL), and ethanol plus Silymarin (ET + 100 mg/kg SLY). The levels of serum urea, creatinine, uric acid, and nitrite oxide (NO) were measured, as were oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT), glutathione (GPx), malondialdehyde (MDA), and inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Then, the kidney organ was harvested for histological study. Results: Citrullus lanatus seed flavonoids (FCL) substantially (p < 0.05) reduced ethanol-induced increases in creatinine, urea, and uric acid. When rats administered FCL were compared to untreated ethanol rats, there was a significant increase (p < 0.05) in CAT, SOD, and GPx levels, as well as decreased MDA. FCL significantly reduced IL-1β and TNF-α levels in ethanol-treated rats. A histological examination significantly corroborated the biochemical assay result. Conclusions: The findings of this study show that the flavonoid-rich fraction of Citrullus lanatus seed has therapeutic potential against ethanol-induced kidney injury by lowering the rise in renal function, inflammatory markers, and oxidative stress. As a result, FCL may work as a plant-based natural therapy to minimise kidney damage. As a result, in the preclinical context, FCL has the potential to minimise organ toxicity for oral therapeutic purposes.
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