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

Summya Rashid, Nemat Ali, Sana Nafees, Syed Kazim Hasan, Sarwat Sultana

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalFood and Chemical Toxicology
Volume66
DOIs
StatePublished - Apr 2014
Externally publishedYes

Keywords

  • 5-FU
  • Apoptosis
  • CH
  • KIM-1
  • Oxidative stress

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