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Evaluating the protective effect of resveratrol, Q10, and alpha-lipoic acid on radiation-induced mice spermatogenesis injury: A histopathological study.

ABSTRACT: Background:Testis is one of the most sensitive organs against the toxic effect of ionizing radiation. Exposure to even a low dose of radiation during radiotherapy, diagnostic radiology, or a radiological event could pose a threat to spermatogenesis. This may lead to temporary or permanent infertility or even transfer of genomic instability to the next generations. Objective:In this study, we evaluated the protective effect of treatment with three natural antioxidants; resveratrol, alpha lipoic acid, and coenzyme Q10 on radiation-induced spermatogenesis injury. Materials and Methods:30 NMRI mice (6-8 wk, 30 ± 5 gr) were randomly divided into six groups (n = 5/each) as 1) control; 2) radiation; 3) radiation + resveratrol; 4) radiation + alpha lipoic acid; 5) radiation + resveratrol + alpha lipoic acid; and 6) radiation+ Q10. Mice were treated with 100 mg/kg resveratrol or 200 mg/kg alpha lipoic acid or a combination of these drugs. Also, Q10 was administered at 200 mg/kg. All treatments were performed daily from two days before to 30 min before irradiation. Afterward, mice were exposed to 2 Gy 60 Co gamma rays; 37 days after irradiation, the testicular samples were collected and evaluated for histopathological parameters. Results:Results showed that these agents are able to alleviate some toxicological parameters such as basal lamina and epididymis decreased sperm density. Also, all agents were able to increase Johnsen score. However, they could not protect against radiation-induced edema, atrophy of seminiferous tubules, and hyperplasia in Leydig cells. Conclusion:This study indicates that resveratrol, alpha-lipoic acid, and Q10 have the potential to reduce some of the side effects of radiation on mice spermatogenesis. However, they cannot protect Leydig cells as a source of testosterone and seminiferous tubules as the location of sperm maturation.

SUBMITTER: Najafi M

PROVIDER: S-EPMC6943799 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:Cisplatin, a small platinum-containing molecule, is a widely used, highly effective anticancer drug. However, severe side effects have been found in cancer patients treated with cisplatin, including nephrotoxicity, neurotoxicity, and ototoxicity. These cisplatin-induced side effects can have a major impact on patient quality of life, including social development problems in pediatric patients that develop hearing loss. Previous studies have suggested that the major cause of cisplatin-induced ototoxicity is abnormal accumulation of reactive oxygen species (ROS) and oxidative stress. Alpha-lipoic acid (ALA), one of the most effective antioxidants, is known to be involved in the cellular antioxidant system and may have a protective effect on cisplatin-induced ototoxicity. However, the therapeutic effect of ALA on damaged hearing function and its detailed mechanism of action are not fully understood. This study focused on determining whether ALA has a potential as a protective and/or therapeutic agent for cisplatin-induced ototoxicity. Histological and physiological analyses were performed using cisplatin-treated mouse cochlea and HEI-OC1 culture cells in pre- and post-treatment with ALA in vitro and in vivo. We found that ALA contributes to protecting mitochondrial function by preventing ROS accumulation and inhibiting apoptotic cell death. Importantly, post-treatment with ALA consistently showed an almost equal restorative effect to pretreatment, in vitro and in vivo, supporting the possible use of ALA as a therapeutic agent for cisplatin-induced ototoxicity. This study is the first report on a strong therapeutic potential of ALA to rescue ototoxic hearing loss caused by cisplatin, and our data provide key evidence that ALA may act as a reducing agent for glutathione disulfide to increase glutathione levels on behalf of glutathione reductase. This result was consistent in both cultured cells and the mouse model, which improves the clinical value of ALA for therapy of cisplatin-induced ototoxicity.

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Evaluating the protective effect of resveratrol, Q10, and alpha-lipoic acid on radiation-induced mice spermatogenesis injury: A histopathological study.

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