Protective effects of cilostazol against cisplatin-induced hepatorenal toxicity in male mice

Elham Hakimizadeh, Fatemeh Khajehasani, Morteza Amirteimoury, Ayat Kaeidi, Jalal Hassanshahi, Iman Fatemi

Abstract


Background and purpose: Cisplatin (CPN) is a widely used and potent chemotherapy drug for cancer treatment. However, one of the major side effects of CPN is hepatorenal toxicity. Recently, cilostazol (CSZ), a type III phosphodiesterase inhibitor, has promising effects against liver and kidney toxicities. We assessed the effects of CSZ against CPN-induced hepatorenal toxicity (CIHR) in male mice.

Experimental approach: Twenty-four male mice were randomly assigned as follows: control group (no treatment), CPN group (treated with 20 mg/kg CPN on day one of the experiment), and CPN + CSZ 3 and                  15 groups (treated with CPN on day one of the experiment plus CSZ (3 and 15 mg/kg) orally for four days). Biochemical, oxidative, and histological investigations were conducted to evaluate the effectiveness of CSZ in protecting the liver and kidneys from CPN-induced damage.

Findings/Results: The results showed that treatment with CSZ, especially at 15 mg/kg, significantly reduced the CPN-induced increase in serum concentrations of biochemical markers such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine. Furthermore, CSZ treatment at 15 mg/kg also restored the hepatorenal oxidative stress factors, including superoxide dismutase, malondialdehyde, and glutathione peroxidase. Histological examination revealed a significant improvement in groups receiving CSZ (15 mg/kg) compared to the CPN-treated group, alongside biochemical and oxidative results.

Conclusion and implications: The findings of this investigation point towards the potential of CSZ as a viable contender for subsequent exploration in the realm of devising efficacious therapeutic approaches for CIHR.

Keywords: Cilostazol; Cisplatin; Kidney; Liver; Oxidative stress.


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References


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