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Article Publish Status: FREE
Abstract Title:

Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity.

Abstract Source:

Iran J Basic Med Sci. 2019 Feb ;22(2):179-186. PMID: 30834084

Abstract Author(s):

Saeed Nazari Soltan Ahmad, Nadereh Rashtchizadeh, Hassan Argani, Leila Roshangar, Amir Ghorbanihaghjo, Davoud Sanajou, Fatemeh Panah, Zahra Ashrafi Jigheh, Siavoush Dastmalchi, Ashkan Kalantary-Charvadeh

Article Affiliation:

Saeed Nazari Soltan Ahmad

Abstract:

Objectives: 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.

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