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Boswellic Acid and Betulinic Acid Pre-treatments Can Prevent the Nephrotoxicity Caused by Cyclophosphamide Induction

  • BIOCHEMISTRY, BIOPHYSICS, AND MOLECULAR BIOLOGY
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Abstract

Cyclophosphamide (CYP) is a chemotherapeutic drug used to treat various cancers. However, its clinical use is limited due to severe organ damage, particularly to the kidneys. While several phytochemicals have been identified as potential therapeutic targets for CYP nephrotoxicity, the nephroprotective effects of boswellic acid (BOSW) and betulinic acid (BET) have not yet been investigated. Our study used 42 rats divided into six equal groups. The study included six groups: control, CYP (200 mg/kg), CYP+BOSW20 (20 mg/kg), CYP+BOSW40 (40 mg/kg), CYP+BET20 (20 mg/kg), and CYP+BET40 (40 mg/kg). The pre-treatments with BOSW and BET lasted for 14 days, while the application of cyclophosphamide was performed intraperitoneally only on the 4th day of the study. After the experimental protocol, the animals were sacrificed, and their kidney tissues were isolated. Renal function parameters, histological examination, oxidative stress, and inflammation parameters were assessed both biochemically and at the molecular level in kidney tissue. The results showed that oxidative stress and inflammatory response were increased in the kidney tissue of rats treated with CYP, leading to impaired renal histology and function parameters (p < 0.05). Oral administration of both doses of BET and especially high doses of BOSW improved biochemical, oxidative, and inflammatory parameters significantly (p < 0.05). Histological studies also showed the restoration of normal kidney tissue architecture. BOSW and BET have promising biological activity against CYP-induced nephrotoxicity by attenuating inflammation and oxidative stress and enhancing antioxidant status.

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ACKNOWLEDGMENTS

The authors would like to thank Dr. Ömer Türkmen for English language editing of the manuscript.

Funding

This research was financially supported by the Office of Scientific Research Projects of Van Yuzuncu Yil University under grant no. TYL-2021-9077.

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Mehmet Berköz and Oğuzhan Çiftçi contributed equally to literature review, project administration, animal studies, laboratory analysis, statistical analysis, and writing of the manuscript. Mehmet Berköz contributed to statistical analysis and reviewing of the manuscript. All authors read and approved the manuscript.

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Correspondence to Mehmet Berköz.

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This work does not contain any studies involving human and animal subjects. Data analysis was performed from the open-access database Pulse Transit Time PPG Dataset (version 1.1.0) [9]. According to the Pulse Transit Time PPG Dataset data, all studies were conducted in accordance with the principles of biomedical ethics set out in the 1964 Declaration of Helsinki and its subsequent amendments, and all participants provided written informed consent.

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Berköz, M., Çiftçi, O. Boswellic Acid and Betulinic Acid Pre-treatments Can Prevent the Nephrotoxicity Caused by Cyclophosphamide Induction. Dokl Biochem Biophys (2024). https://doi.org/10.1134/S1607672924600234

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