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N-乙酰半胱氨酸通过调节炎性细胞因子、类固醇和抗氧化活性对赤霉素诱导的睾丸功能障碍的影响。

Impacts of n-acetyl cysteine on gibberellic acid-induced testicular dysfunction through regulation of inflammatory cytokines, steroid and antioxidant activity.

作者信息

Soliman Mohamed Mohamed, Aldhahrani Adil, Gaber Ahmed, Alsanie Walaa F, Shukry Mustafa, Mohamed Wafaa Abdou, Metwally Mohamed M M, Mohamed Alaa Ahmed

机构信息

Clinical Laboratory Sciences Department, Turabah University College, Taif University, Taif, Saudi Arabia.

Department of Biology, College of Science, Taif University, Taif, Saudi Arabia.

出版信息

Andrologia. 2021 Jun;53(5):e14036. doi: 10.1111/and.14036. Epub 2021 Mar 16.

Abstract

In agriculture, gibberellic acid (GA3) is commonly used with extreme dangers for public health. The current research evaluates the improving effects of n-acetyl cysteine (NAC, 150 mg/kg bw) co-administered with GA3 (55 mg/kg bw) mediated testicular injury. Twenty-four male albino rats were split into 4 groups: Negative control (CNT), NAC group, positive GA3 group and protective group, co-administered NAC plus GA3. On day 21, rats were anesthetised then euthanised by decapitation. Blood samples were collected; testicular samples were taken for semen analysis, serum chemistry, RNA extraction, histological and antioxidants markers examination. Our results revealed a significant decline p < .05 of catalase level and total antioxidant capacity. There was a substantial rise of MDA concentration in GA3-treated rats along with a considerable decrease of the antioxidant markers (SOD, GSH) and serum male reproductive hormones. In GA3-treated rats, an overexpression of the inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokine IL-10 with boost mRNA expression of nuclear factor-kappa (NF B) were confirmed. There was downregulation of steroidogenesis genes and decrease in sperm quality and concentration with an increase in sperm abnormalities, all were reported in GA3-treated rats. NAC treatment significantly increased the antioxidant state, testicular function beside structural germ cell and seminiferous tubules histology accompanied by upsurge of steroidogenic mRNA expressions (P450scc and 3β-HSD) and downregulated the pro-inflammatory cytokines mRNA expression (TNF-α, IL-1β). These results confirm the antioxidant capability of NAC and afford robust evidence about the ameliorative effect of the NAC to attenuate the testicular injury induced by GA3 through modulation of the antioxidant defence system, steroidogenic and pro-inflammatory cytokines mRNA expression.

摘要

在农业中,赤霉酸(GA3)被普遍使用,对公众健康存在极大危害。当前研究评估了与GA3(55毫克/千克体重)共同给药的N-乙酰半胱氨酸(NAC,150毫克/千克体重)对睾丸损伤的改善作用。将24只雄性白化大鼠分为4组:阴性对照组(CNT)、NAC组、阳性GA3组和保护组(NAC与GA3共同给药)。在第21天,将大鼠麻醉后断头处死。采集血样;取睾丸样本进行精液分析、血清化学检测、RNA提取、组织学检查以及抗氧化剂标志物检测。我们的结果显示,过氧化氢酶水平和总抗氧化能力显著下降(p < 0.05)。GA3处理的大鼠中丙二醛浓度大幅升高,同时抗氧化标志物(超氧化物歧化酶、谷胱甘肽)和血清雄性生殖激素显著降低。在GA3处理的大鼠中证实了炎性细胞因子(肿瘤坏死因子-α、白细胞介素-1β)的过度表达以及抗炎细胞因子白细胞介素-10的表达,同时核因子-κB的mRNA表达增强。GA3处理的大鼠中,类固醇生成基因下调,精子质量和浓度降低,精子异常增加。NAC治疗显著提高了抗氧化状态、睾丸功能,改善了生精细胞和生精小管的结构组织学,同时类固醇生成mRNA表达(细胞色素P450侧链裂解酶和3β-羟基类固醇脱氢酶)增加,促炎细胞因子mRNA表达(肿瘤坏死因子-α、白细胞介素-1β)下调。这些结果证实了NAC的抗氧化能力,并有力地证明了NAC通过调节抗氧化防御系统、类固醇生成和促炎细胞因子mRNA表达来减轻GA3诱导的睾丸损伤的改善作用。

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