Assessment of the In Vivo Reprotoxicity of Isotretinoin in Sprague-Dawley Male Rat.

Q3 Pharmacology, Toxicology and Pharmaceutics

Current drug discovery technologies Pub Date : 2024-01-01 DOI:10.2174/1570163820666230816155855

Ahmad Khalil, Mai Daradkeh, Amneh Alrabie, Hasan Abo Siam

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引用次数: 0

Abstract

Background: Isotretinoin (ISO) belongs to a family of drugs called retinoids. It is the most effective drug prescribed by dermatologists for the treatment of the inflammatory disease, acne vulgaris. A significant barrier to the use of ISO has worries regarding its adverse effect profile. Despite the well-recognized reproductive toxicity and teratogenicity in females, there is no warning related to the use by male patients in the medication prospectus. Current data on the effects on human male fertility is contradictory and inconclusive.

Objectives: This study was undertaken to investigate the potential effects of ISO oral doses in the Sprague-Dawley male rat germ cells using the sperm morphology assay. Also, the serum levels of the follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured.

Methods: The rat groups were given varying ISO doses via gastric gavage for seven consecutive days. The epididymis sperm specimens were microscopically examined for the following reproductive toxicity parameters: sperm concentration, examined viability, motility, and morphology. The serum FSH, LH, and testosterone levels were measured by using the corresponding enzyme-linked immunosorbent assay (ELISA) kit. The data were analyzed statistically by one-way analysis of variance (ANOVA) followed by the Tukey test at P ≤ 0.05 significance level.

Results: The results indicated that the drug did not significantly increase the sex hormone levels but notably affected both the sperm quantity and quality.

Conclusion: These observations suggest that ISO was reprotoxic, and future therapies should be further reassessed.

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在 Sprague-Dawley 雄性大鼠体内评估异维A酸的生殖毒性

背景：异维A酸（ISO）属于维甲酸类药物。它是皮肤科医生治疗炎症性疾病--寻常痤疮的最有效药物。使用 ISO 的一大障碍是对其不良反应的担忧。尽管对女性的生殖毒性和致畸性已得到公认，但在药品说明书中却没有关于男性患者使用的警告。目前有关该药对男性生育能力影响的数据相互矛盾，尚无定论：本研究采用精子形态测定法，调查 ISO 口服剂量对 Sprague-Dawley 雄性大鼠生殖细胞的潜在影响。此外，还测定了血清中卵泡刺激素（FSH）、黄体生成素（LH）和睾酮的水平：方法：给大鼠组连续七天灌胃不同剂量的 ISO。对附睾精子标本进行显微镜检查，以确定以下生殖毒性参数：精子浓度、存活率、活力和形态。使用相应的酶联免疫吸附试验（ELISA）试剂盒测定血清 FSH、LH 和睾酮水平。数据采用单因素方差分析（ANOVA）和Tukey检验进行统计分析，显著性水平为P≤0.05：结果表明，药物并未明显提高性激素水平，但对精子的数量和质量均有显著影响：这些观察结果表明，ISO具有生殖毒性，今后的治疗方法应进一步重新评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug discovery technologies Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

3.70

自引率

0.00%

发文量

期刊介绍： Due to the plethora of new approaches being used in modern drug discovery by the pharmaceutical industry, Current Drug Discovery Technologies has been established to provide comprehensive overviews of all the major modern techniques and technologies used in drug design and discovery. The journal is the forum for publishing both original research papers and reviews describing novel approaches and cutting edge technologies used in all stages of drug discovery. The journal addresses the multidimensional challenges of drug discovery science including integration issues of the drug discovery process.