Biochemistry Division and GTMR Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Chem Biol Interact. 2016 Oct 25;258:205-13. doi: 10.1016/j.cbi.2016.09.008. Epub 2016 Sep 9.
Despite the efficacy of cisplatin as a chemotherapeutic agent against various cancers, its clinical utility is limited by serious adverse reactions including nephrotoxicity.
The current study aims to investigate the protective potential of tangeretin, a citrus flavone with marked antioxidant actions, against cisplatin-induced renal injury in rats.
Tangeretin was administered at 50 and 100 mg/kg p.o. for 1 week starting one day before cisplatin (7.5 mg/kg i.p.) injection. Likewise, silymarin was administered at 100 mg/kg orally. Renal function tests, histopathology, oxidative stress and inflammatory events were investigated.
Tangeretin mitigated the increased levels of serum creatinine, blood urea nitrogen and histopathologic alterations evoked by cisplatin. It alleviated renal oxidative stress due to cisplatin by lowering lipid peroxides, nitric oxide and Nrf2 levels with concomitant enhancement of GSH and GPx. Tangeretin also suppressed the upregulated inflammatory response seen with cisplatin treatment by downregulation of activated NF-κB p65 protein expression together with its downstream effectors e.g., iNOS and TNF-α, with restoration of the anti-inflammatory interleukin IL-10. Additionally, it down-regulated the expression of caspase-3, an apoptotic marker, thus favoring renal cell survival. Importantly, tangeretin enhanced the cytotoxic actions of cisplatin in Hep3B and HCT-116 human cancer cell lines.
Together, these findings accentuate the dual benefit of tangeretin: mitigation of renal injury-induced by cisplatin and enhancement of its cytotoxic effects.
尽管顺铂作为一种针对各种癌症的化疗药物具有疗效，但由于其严重的不良反应，包括肾毒性，其临床应用受到限制。
本研究旨在探讨具有明显抗氧化作用的柑橘黄酮橙皮素对顺铂诱导的大鼠肾损伤的保护潜力。
橙皮素以 50 和 100mg/kg 口服给药，于顺铂（7.5mg/kg 腹腔注射）注射前一天开始给药 1 周。同样，给予水飞蓟素 100mg/kg 口服。检测肾功能、组织病理学、氧化应激和炎症事件。
橙皮素减轻了顺铂引起的血清肌酐、血尿素氮和组织病理学改变的增加水平。它通过降低脂质过氧化物、一氧化氮和 Nrf2 水平，同时增强 GSH 和 GPx，减轻了顺铂引起的肾氧化应激。橙皮素还通过下调激活的 NF-κB p65 蛋白表达及其下游效应物，如 iNOS 和 TNF-α，同时恢复抗炎细胞因子 IL-10，抑制了顺铂治疗引起的上调的炎症反应。此外，它下调了凋亡标志物 caspase-3 的表达，从而有利于肾细胞存活。重要的是，橙皮素增强了顺铂在 Hep3B 和 HCT-116 人癌细胞系中的细胞毒性作用。
这些发现强调了橙皮素的双重益处：减轻顺铂引起的肾损伤和增强其细胞毒性作用。
