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阿齐沙坦对环磷酰胺诱导的大鼠模型卵巢毒性的保护作用。

Protective effects of Azilsartan against cyclophosphamide-induced ovarian toxicity in rats model.

作者信息

Mahmood Naza Mohammed Ali

机构信息

Department of Pharmacology & Toxicology, College of Pharmacy, University of Sulaimani, Madam Meteeran Street, Sulaimaniyah 0046, Iraq.

出版信息

Toxicol Res (Camb). 2024 Mar 4;13(2):tfae027. doi: 10.1093/toxres/tfae027. eCollection 2024 Apr.

Abstract

BACKGROUND

Cyclophosphamide (CP) is an effective alkylating anticancer agent that is widely used in cancer chemotherapy, and it can cause ototoxicity and infertility in women.

OBJECTIVES

So, this study aimed to evaluate the protective effects of Azilsartan (AZ) as an antioxidant and anti-inflammatory agent in a rat model of CP-induced ovarian toxicity.

MATERIALS AND METHODS

After receiving the 28 female Wister rats, they were acclimatized in proper environmental conditions for a week and then randomly divided into four groups based on the study protocol. After 15 days of the experiment, they were sacrificed, and organs were collected for biomarker detection (Using the ELISA technique) and histopathological analysis.

RESULTS

The level of IL-10 was significantly ( < 0.05) decreased in all treated groups compared to control hostile groups, while the TNF-α level was significantly ( < 0.05) increased in AZ (220.67 ± 7.88 ng/mL) and AZ + CP groups (221.78 ± 9.11 ng/mL) compared to control negative/CP groups. Regarding the oxidative biomarker level, a significant increase was only found in the AZ + CP group (176.02 ± 6.71 nmol/mL) compared to the control negative group. On the other hand, histopathological findings revealed that ovarian sections in animals that received a single dose of CP had severe ovarian atrophy with significant follicular regression and deterioration, as well as depletion of stromal supportive tissues.

CONCLUSIONS

Azilsartan drastically reduced CP-induced ovarian toxicity in vivo by enhancing oxidative stress and inhibiting inflammatory effects in ovarian cells.

摘要

背景

环磷酰胺(CP)是一种有效的烷化剂抗癌药物,广泛应用于癌症化疗,它可导致女性耳毒性和不孕。

目的

因此,本研究旨在评估阿齐沙坦(AZ)作为一种抗氧化和抗炎剂对CP诱导的大鼠卵巢毒性模型的保护作用。

材料与方法

将28只雌性Wistar大鼠接收后,在适宜环境条件下适应一周,然后根据研究方案随机分为四组。实验15天后,将它们处死,收集器官用于生物标志物检测(使用ELISA技术)和组织病理学分析。

结果

与对照不良组相比,所有治疗组的IL-10水平均显著(<0.05)降低,而与对照阴性/CP组相比,AZ组(220.67±7.88 ng/mL)和AZ+CP组(221.78±9.11 ng/mL)的TNF-α水平显著(<0.05)升高。关于氧化生物标志物水平,与对照阴性组相比,仅在AZ+CP组(176.02±6.71 nmol/mL)中发现显著升高。另一方面,组织病理学结果显示,接受单剂量CP的动物的卵巢切片出现严重的卵巢萎缩,伴有明显的卵泡退化和恶化,以及基质支持组织的消耗。

结论

阿齐沙坦通过增强氧化应激和抑制卵巢细胞中的炎症作用,在体内显著降低了CP诱导的卵巢毒性。

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