Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage

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• 作者：Bidya Dhar Sahu^a ; Madhusudana Kuncha^a ; G. Jeevana Sindhura^b ; Ramakrishna Sistla^a ; ^{sistla@iict.res.in}
• 关键词：Ac-DEVD-AMC ; acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin ; BUN ; blood urea nitrogen ; BW ; body weight ; CAT ; catalase ; DCFH-DA ; 2 ; 7-dichlorofluorescein diacetate ; DTNB ; 5 ; 5-dithio-bis (2-nitrobenzoic acid) ; NED ; N-(1-naphthyl)-ethylene-diamine dihydrochl
• 刊名：Phytomedicine
• 出版年：2013
• 出版时间：15 March, 2013
• 年：2013
• 卷：20
• 期：5
• 页码：453-460
• 全文大小：1360 K

文摘

Nephrotoxicity is an important complication in cancer patients undergoing cisplatin therapy. Oxidative stress, inflammation and apoptosis/necrosis are the major patho-mechanisms of cisplatin induced nephrotoxicity. In the present study, hesperidin, a naturally-occurring bioflavonoid has been demonstrated to have protective effect on cisplatin-induced renal injury in rats. Cisplatin intoxication resulted in structural and functional renal impairment which was revealed by massive histopathological changes and elevated blood urea nitrogen and serum creatinine levels, respectively. Renal injury was associated with oxidative stress/lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation with decreased levels of antioxidants such as reduced glutathione, vitamin C, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase. Cisplatin administration also triggered inflammatory response in rat kidneys by inducing pro-inflammatory cytokine, TNF-¦Á, with the increased expression of myeloperoxidase (MPO). Furthermore, cisplatin increased the activity of caspase-3 and DNA damage with decreased tissue nitric oxide levels. Hesperidin treatment significantly attenuated the cisplatin-induced oxidative stress/lipid peroxidation, inflammation (infiltration of leukocytes and pro-inflammatory cytokine), apoptosis/necrosis (caspase-3 activity with DNA damage) as well as increased expression of nitric oxide in the kidney and improved renal function. Thus, our results suggest that hesperidin co-administration may serve as a novel and promising preventive strategy against cisplatin-induced nephrotoxicity.