Pituranthos chloranthus essential oil alleviates cisplatin-induced nephrotoxicity and potentiates antitumor activities: An in vivo and in vitro study

Abstract

Objective: To study the potential of Pituranthos chloranthus essential oil (PC) as a chemoprotective agent.

Methods: In the in vitro study, cell proliferation were determined in CT26, SW620, and SW480 cells. Cells were exposed to in-creasing concentrations of PC (0, 6.25, 12.5, 25, 50, 100, and 200 μg/mL). Combination index was calculated by applying the Chou-Talalay method, apoptopsis was analyzed by annexin V/propidium iodide staining, reactive oxygen species accumulation, and the Δψm drop were also assessed. In the in vivo study, mice were divided into 5 groups: the normal control group, the CT26 tumor-bearing group, the CT26 tumor-bearing mice+PC group, the CT26 tumor-bearing mice+cisplatin group, and the CT26 tumor-bearing mice+cisplatin+PC group. Organ coefficients and tumor volume were calculated. Alanine aminotransferase, aspartate aminotransferase, creatinine, and tumor necrosis factor-a levels were assessed.

Results: Cisplatin with PC induced a synergistic effect, allowing for reduced cisplatin dose while maintaining the same therapeutic efficacy. PC-cisplatin combinations inhibited cell viability by significantly inducing apoptosis, increasing reactive oxygen species accumulation and reducing mitochondrial membrane potential. Co-treatment with cisplatin and PC restored organ coefficients, reduced tumor volume, and alleviated nephrotoxicity in CT26 tumor-bearing mice by restoring kidney function markers and ameliorating kidney inflammation status.

Conclusions: PC shows a chemoprotective potential by enhancing the antitumor effect of cisplatin while alleviating its side effects.

Keywords

Pituranthos chloranthus / Cisplatin / Chemoprotective agent / CT26 tumor-bearing mice / Colorectal cancer / Toxicity

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This research was funded by The Tunisian Ministry of Research and Higher Education.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

AL performed the experiments and wrote the manuscript. JB performed the revision and the editing of the manuscript. FS helped in cytotoxicity tests. MN helped in histological analysis. AS and MS helped in the in vivo experiment. LCG supervised the overall project.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors express their gratitude to the Tunisian Ministry of Higher Education and Scientific Research for the funding provided for this study.

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