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Objective(s): Cisplatin is an effective antineoplastic agent; its clinical utility, however, is limited by a few salient toxic side effects like nephrotoxicity. This study aimed to determine the potential protective effects of tangeretin, a citrus-derived flavonoid, against renal tubular cell injury in cisplatin-induced renal toxicity of rats. Materials and Methods: Tangeretin was injected intraperitoneally at 2.5 and 5 mg/kg doses for 10 days, and a single dose of cisplatin (8 mg/kg) was injected on the 7th day. Tests of kidney function and tubular injury in renal tissues and urine together with oxidative stress and inflammation markers were examined. Results: Tangeretin ameliorated cisplatin-induced elevations in serum creatinine, BUN, and histopathologic changes. It also attenuated kidney oxidative stress elicited by cisplatin as demonstrated by reduced MDA and increased GSH, CAT, and SOD activities, elevated Nrf2 expression and protein levels of its downstream effectors, HO-1 and NQO-1. Tangeretin further alleviated inflammation evoked by cisplatin as indicated by reduced NF-κB p65 subunit phosphorylation with a simultaneous decrement in its downstream effectors IL-1β and TNF-α expression and protein levels. Moreover, it declined caspase-3 protein levels and TUNEL positive cells in the kidneys, the markers of apoptosis and DNA fragmentation, thus improving renal endurance. Additionally, tangeretin mitigated renal levels of KIM-1 and NGAL, as well as urinary cystatin C and β2-microglobulin concentrations, the markers of renal tubular injury. Conclusion: Collectively, these data signify the binary profit of tangeretin: enhancement of renal protective mechanisms against cisplatin and attenuation of renal tubular cell injuries induced by the agent. [ABSTRACT FROM AUTHOR]

Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed. Dunnione repressed cisplatin-induced inflammation in the kidneys as indicated by decreased TNF-α/IL-1β levels, and reduced nuclear phosphorylated NF-κB p65. This agent also obviated cisplatin-invoked oxidative stress as elucidated by decreased MDA/GSH levels and increased SOD/CAT activities. Dunnione, furthermore, improved renal histological deteriorations as well as caspase-3 activities and terminal deoxynucleotidyl transferase (TUNEL) positive cells, the indicators of apoptosis. Moreover, it up-regulated nuclear Nrf2 and cytosolic haeme-oxygenase-1 (HO-1) and NQO1 levels; meanwhile, promoted NAD+/NADH ratios followed by enhancing the activities of Sirt1 and PARP1; and further attenuated nuclear acetylated NF-κB p65. Dunnione additionally declined cisplatin-evoked retrogression in renal function and upraise in urinary markers of glomerular and tubular injury as demonstrated by decreased serum urea and creatinine with simultaneous reductions in urinary excretions of collagen type IV, podocin, cystatin C, and retinol-binding protein (RBP). Altogether, these findings offer dunnione as a potential protective agent against cisplatin-induced nephrotoxicity in rats. [ABSTRACT FROM AUTHOR]