Cilostazol attenuates mirabegron-induced hepatic and renal toxicity in rats: regulation of metabolic, oxidative, and inflammatory pathways

Abstract

Background

Mirabegron (MIRG) is a type of β3 adrenoceptor agonist that is considered an alternative therapy for the treatment of overactive bladder (OAB) symptoms. Cilostazol (CITZ) is a selective inhibitor of phosphodiesterase (III) that has various pharmacological effects.

Objectve

The current study aimed to highlight the regulatory effects of CITZ on MIRG-induced toxicity.

Materials and Methods

Male rats were divided into six groups. Blood samples were collected to determine different hepatic and kidney function levels along with serum protein electrophoresis and inflammatory factor levels. Histopathological studies and oxidative stress (OS) were also assessed. Kidney and hepatic damage were detected following the administration of MIRG, especially at high doses, due to elevated OS, inflammation, and apoptotic marker levels.

Results

Rats receiving CITZ exhibited significant improvements in both hepatic and kidney functions, with decreased inflammation and OS.

Conclusion

CITZ administration plays a beneficial role in alleviating hepatic and nephrotoxicity induced by MIRG by inhibiting OS and inflammation.

Keywords:

• β3 Adrenoceptor agonist
• liver injury
• renal damage
• oxidative stress
• inflammation

Acknowledgements

None.

CRediT authorship contribution statement

[MMA] and [IMIL] contributed to the study conception and design. Material preparation, data collection and analysis were performed by [MMA] and [IMIL]. [MMA] and [IMIL] estimated the whole biological parameters. The first draft of the manuscript was written by [MMA]. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The animal experimental design was approved by the Animal Research and Ethical Committee of the National Organisation of Drug Control and Research (NODCAR) approval number (NODCAR/II/7/2023). All authors read and approved the manuscript.

Consent for publication

All authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

The obtained data analysed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.