Ahmed Zheen Aorahman, Abtar Aso Nihad, Othman Hemn Hassan, Aziz Tavga Ahmed
Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq.
Department of Anatomy and Pathology, College of Veterinary Medicine, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq.
Drug Des Devel Ther. 2019 Sep 20;13:3321-3329. doi: 10.2147/DDDT.S222127. eCollection 2019.
This study aimed to evaluate the effect of quercetin and/or sitagliptin on testicular damage induced by doxorubicin (DOX).
Twenty-five male Wistar rats, weighing 240±20 g, were randomly divided into five groups as follows: a negative control group; that was treated with 1 mL of 0.9% sodium chloride; a DOX-treated group received Intraperitoneal (I.P.) DOX injection (3 mg/kg); a group treated with quercetin 80 mg/kg + sitagliptin 10 mg/kg + DOX; a group treated with quercetin 80 mg/kg + DOX; and a group treated with sitagliptin 10 mg/kg+ DOX. All treatment were given orally daily for 21 days with I.P. DOX 3 mg/kg injection for the treatment groups at days 8, 10, 12, 15, 17, and 19. On day 22, blood was collected for analysis of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutathione peroxidase (GPx), and total antioxidant capacity (TAOC). The testes were also removed and sent for histopathological examination.
The study revealed that the combination of quercetin with sitagliptin produced a significant increase in testosterone and FSH levels with a non-significant increase in LH level. This combination also non-significantly decreased the level of ALP and LDH and restored the GPx level with enhancing TAOC.
The results suggest quercetin/sitagliptin combination as a promising therapeutic modality for attenuation of DOX-induced testicular toxicity in rats, and the main mechanism involved in such effect could be due to the antioxidant and anti-inflammatory properties of both agents.
本研究旨在评估槲皮素和/或西他列汀对阿霉素（DOX）诱导的睾丸损伤的影响。
将25只体重240±20克的雄性Wistar大鼠随机分为五组，如下：阴性对照组，用1毫升0.9%氯化钠处理；DOX处理组接受腹腔注射（I.P.）DOX（3毫克/千克）；一组用80毫克/千克槲皮素+10毫克/千克西他列汀+DOX处理；一组用80毫克/千克槲皮素+DOX处理；一组用10毫克/千克西他列汀+DOX处理。所有处理均每日口服给药21天，处理组在第8、10、12、15、17和19天腹腔注射3毫克/千克DOX。在第22天，采集血液分析睾酮、黄体生成素（LH）、卵泡刺激素（FSH）、碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）、谷胱甘肽过氧化物酶（GPx）和总抗氧化能力（TAOC）。同时取出睾丸送去进行组织病理学检查。
研究表明，槲皮素与西他列汀联合使用可使睾酮和FSH水平显著升高，LH水平升高不显著。这种联合用药还使ALP和LDH水平非显著降低，并通过提高TAOC恢复了GPx水平。
结果表明，槲皮素/西他列汀联合用药有望成为减轻大鼠DOX诱导的睾丸毒性的治疗方式，这种作用的主要机制可能是由于两种药物的抗氧化和抗炎特性。
