Olmesartan attenuates doxorubicin-elicited testicular toxicity: The interaction between sirtuin-1, HMGB1/NLRP3 inflammasome/gasdermin D signaling, and AMPK/mTOR-driven autophagy.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-03-07 DOI:10.1016/j.lfs.2025.123545

Hemat A Elariny, Hanan Abdelmawgoud Atia, Marwa H Abdallah, Amany M Khalifa, Maaly A Abd Elmaaboud, Mennatallah A Elkady, Ahmed M Kabel

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Abstract

Background: In the recent years, there has been an increased incidence of testicular toxicity associated with doxorubicin (DOX) use in cancer therapy. The mechanisms of this adverse effect may include induction of oxidative stress with augmentation of the inflammatory and the apoptotic signals in the testicular tissues. The ongoing research is directed towards the exploration of new agents that are capable of overcoming this health problem. This study was a trial to evaluate the efficacy of Olmesartan as a protective agent against DOX-induced testicular dysfunction in male rats.

Materials and methods: Forty adult male Sprague-Dawley rats were divided into control group, DOX-injected group, and three DOX-injected groups treated with olmesartan at 3 dose levels (1, 5, and 10 mg/kg/day). The effect of the different treatments was assessed at the biochemical and the morphological levels.

Key findings: Olmesartan administered to DOX-treated rats induced dose-dependent restoration of the testicular weight and functions, normalization of the hormonal profile, augmentation of the antioxidant defenses, and potentiation of AMPK/mTOR-driven autophagy in comparison to rats treated with DOX alone. These effects were accompanied with a dose-dependent significant mitigation of the cellular events related to pyroptosis and inflammation and a significant amelioration of the testicular morphological changes induced by DOX.

Significance: Olmesartan may represent a promising therapy for DOX-elicited testicular dysfunction, possibly via dose-dependent antioxidant, anti-pyroptotic, anti-inflammatory, and autophagy enhancing effects.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.