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Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis

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Abstract

Cyclophosphamide (CYP) is a chemotherapeutic agent used in the treatment of autoimmune disorders and malignant diseases. However, its usage is restricted due to its severe side effects, especially hepatotoxicity and nephrotoxicity. This study aimed to investigate the protective role of chrysin (CH) against CYP-induced hepatotoxicity and nephrotoxicity in rats. In the present study, 35 male Wistar rats were randomly divided into 5 groups with each group consisting of 7 rats. The rats were pretreated with CH orally in doses of 25- and 50-mg/kg body weight for 7 consecutive days, and CYP (200-mg/kg body weight, i.p.) was administrated on the 7th day 1 h after the last dose of CH. It was found that CH could ameliorate CYP-induced elevations of ALT, ALP, AST, urea, creatinine, MDA, and hepatorenal deterioration, and enhance antioxidant enzymes’ activities such as SOD, CAT, and GPx, and GSH’s level. Furthermore, CH reversed the changes in levels of inflammatory, apoptotic, and autophagic parameters such as NF-κB, TNF-α, IL-1β, IL-6, iNOS, COX-2, Bax, Bcl-2, and LC3B in liver and kidney tissues. To conclude, the findings of this study demonstrated that CH has a protective effect against CYP-induced hepatorenal toxicity.

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Funding

We are grateful to the Bingol University, Scientific Research Projects Coordination Unit, for the financial support for this work (project number BAPSSHMYO. 2016.00.001).

Author information

YT and CC conceived and designed the research. FMK and SK conducted the biochemical analyses. SY performed the histopathological and immunohistochemical analyses. CC and FMK analyzed the data and wrote the manuscript. All authors read and approved the manuscript.

Correspondence to Cuneyt Caglayan.

Ethics declarations

The study was designed and conducted according to ethical norms approved by the Local Animal Experimentation Ethics Committee of the Bingol University (Bingol, Turkey) (approval no. 2016-4/5).

Conflict of interest

The authors declare that they have no conflict of interest.

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Temel, Y., Kucukler, S., Yıldırım, S. et al. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Arch Pharmacol 393, 325–337 (2020). https://doi.org/10.1007/s00210-019-01741-z

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Keywords

  • Apoptosis
  • Chrysin
  • Cyclophosphamide
  • Hepatotoxicity
  • Inflammation
  • Nephrotoxicity