Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats

详细信息    查看全文

• 作者：Summya Rashid ; Nemat Ali ; Sana Nafees ; Syed Kazim Hasan ; Sarwat Sultana ; ^{sarwat786@rediffmail.com" class="auth_mail}
• 关键词：5-FU ; 5-Flourouracil ; CH ; chrysin ; KIM-1 ; kidney injury molecule ; BSA ; bovine serum albumin ; CDNB ; 1-chloro 2 ; 4-dinitrobenzene ; DTNB ; 5 ; 5&prime ; -dithio bis-[2-nitrobenzoic acid] ; EDTA ; ethylene diamine tetra acetic acid ; GPx ; glutathione peroxidase ; GR ; glutathione reductase ; GSH ; reduced glutathione ; GSSG ; oxidized glutathione ; NADPH ; reduced nicotinamide adenine dinucleotide phosphate ; ROS ; reactive oxygen species ; SOD ; superoxide dismutase ; TBA ; thiobarbituric acid ; LDH ; lactate dehydrogenas
• 刊名：Food and Chemical Toxicology
• 出版年：April, 2014
• 年：2014
• 卷：66
• 期：Complete
• 页码：185-193
• 全文大小：2657 K

文摘

5-Fluorouracil (5-FU) is a potent antineoplastic agent commonly used for the treatment of various malignancies. It has diverse adverse effects such as cardiotoxicity, nephrotoxicity and hepatotoxicity which restrict its wide and extensive clinical usage. It causes marked organ toxicity coupled with increased oxidative stress and apoptosis. Chrysin (CH), a natural flavonoid found in many plant extracts, propolis, blue passion flower. It has antioxidative and anti-cancerous properties. The present study was designed to investigate the protective effects of CH against 5-FU induced renal toxicity in wistar rats using biochemical, histopathological and immunohistochemical approaches.

Rats were subjected to prophylactic oral treatment of CH (50 and 100 mg/kg b.wt.) for 21 days against renal toxicity induced by single intraperitoneal administration of 5-FU (150 mg/kg b.wt.). The possible mechanism of 5-FU induced renal toxicity is the induction of oxidative stress; activation of apoptotic pathway by upregulation of p53, bax, caspase-3 and down regulating Bcl-2. However prophylactic treatment of CH decreased serum toxicity markers, increased anti-oxidant armory as well as regulated apoptosis in kidney. Histopathological changes further confirmed the biochemical and immunohistochemical results. Therefore, results of the present finding suggest that CH may be a useful modulator in mitigating 5-FU induced renal toxicity.