LC-ESI-TOF-MS profiling and protective effects of Psidium cattleianum extract against gentamicin-induced nephrotoxicity in rats via Nrf2/HO-1 and caspase-dependent pathway.

Drug-induced nephrotoxicity is an alarming trigger for kidney injury. It is linked to a high rate of illness and fatality, with limited treatment options. Herein, we aimed to unravel the phytochemical profile and understand the protective activity of the aqueous methanolic extract (AME) of P.cattleianum Sabine (Myrtaceae) aerial parts against nephrotoxicity induced by gentamicin (GNT) in rats for the first time. The extract was chromatographed and analyzed using an LC-ESI-TOF-MS system. For the in vivo model, rats received the AME at doses of 200, 400, and 800 mg/kg/day orally for 14 days. The phytochemical results revealed the tentative identification of ninety metabolites, including twelve phenolic acids, fifty-one flavonoids, one proanthocyanidine, one lignan, four coumarins, three terpenes, four organic acids, two stilbenes, seven sugar derivatives, and five miscellaneous compounds. At 800 mg/kg, the AME significantly reduced the KW/BW ratio by 14.7%, BUN by 45.2%, creatinine by 57.6%, and Kim-1 by 57.3%. Oxidative stress markers MDA and 8-OHdG were lowered by 47.5% and 67.4%, respectively, while antioxidant markers GSH and SOD increased by 2.7- and 2.6-fold. The AME also restored HO-1 (4.6-fold increase) and Nrf2 (92.2-fold increase, relative to the GNT-treated group), and suppressed TNF-α, IL-1β, and NF-κB by 53.3%, 64.7%, and 58.9%, respectively. Apoptosis was reduced (Bax ↓64%, cytochrome c ↓58.8%, Bcl-2 ↑threefold), with marked histological improvements confirming nephroprotection. In all, the AME is promoted as an alternative remedy for controlling nephrotoxicity triggered by GNT. However, quantifying and isolating the major constituents and validating the clinical safety are among our future directions.