Protective effects of naringin against oxidative stress, inflammation, apoptosis, and DNA damage in rats with doxorubicin-induced hepatotoxicity

Abstract

Objective: To investigate the protective effects of naringin on doxorubicin (DOX)-induced liver injury.

Methods: A total of 50 male rats were allocated into five groups: the control group, the DOX group, the DOX groups treated with 50 mg/kg and 100 mg/kg of naringin by gastric lavage for 10 days, as well as the group treated with 100 mg/kg of naringin alone. Liver and serum samples were collected for biochemical, histopathological, and molecular analyses, including liver enzyme activity, oxidative stress markers, inflammation, apoptosis-related proteins, and DNA damage indicators.

Results: Naringin attenuated DOX-induced elevation in liver enzyme activity and inflammation markers while enhancing antioxidant activities. Naringin also activated the Nrf2-HO-1 signaling pathway, with the most pronounced effect in the high-dose naringin group. In addition, naringin modulated apoptotic signaling by downregulating the expression of PI3K-AKT and BAX, and upregulating Bcl-2, as well as reduced the level of 8-OHdG. Histopathological evaluation showed that DOX-induced structural liver alterations, such as cellular degeneration and necrosis, were notably attenuated by naringin treatment.

Conclusions: Naringin treatment exerts protective effects against DOX-induced liver injury through its antioxidative, anti-inflammatory, and anti-apoptotic effects.

Keywords

Doxorubicin / Hepatotoxicity / Inflammation / Naringin / Oxidative stress

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This study was supported by the Atatürk University Scientific Research Projects Coordinator (Project No: 2020/8737). We are grateful to Atatürk University, Turkey.

Data availability statement

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

Authors’ contributions

PDA conceived and designed the study, performed data analysis and interpretation, and drafted the manuscript. SY, ES, MW, and ST contributed to data analysis and interpretation and participated in manuscript drafting. FA contributed to data analysis. AC planned the methodology, conducted statistical analysis, critically revised the manuscript, and approved the final version for publication.

Publisher’s note

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

Edited by Liang Q, Tan BJ

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