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Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf‐2/Keap‐1, Inflammatory, Steroidogenic, and Histological Profile
Environmental Toxicology ( IF 4.4 ) Pub Date : 2024-08-24 , DOI: 10.1002/tox.24408
Muhammad Umar Ijaz 1 , Sana Imtiaz 1 , Muhammad Faisal Hayat 1 , Moazama Batool 2 , Khalid A Al-Ghanim 3 , Mian Nadeem Riaz 4
Affiliation  

Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ‐induced testicular toxicity in rats. Forty‐eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2‐related factor 2 (Nrf‐2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap‐1 while downregulating the expression of 3‐beta hydroxysteroid dehydrogenase (3β‐HSD), 17‐beta hydroxysteroid dehydrogenase (17β‐HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin‐6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), nuclear factor‐kappa B (NF‐κB), interleukin‐1beta (IL‐1β), and cyclooxygenase‐2 (COX‐2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate‐specific proteases‐3 (Caspase‐3) and Bcl‐2‐associated X‐protein (Bax) while downregulating the expressions of B‐cell lymphoma‐2 (Bcl‐2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti‐inflammatory, and androgenic potential.

中文翻译:


Sudachitin 通过调节 Nrf-2/Keap-1、炎症、类固醇生成和组织学特征来减轻百草枯引起的白化大鼠睾丸毒性



百草枯 (PQ) 是一种有害除草剂,会对包括男性生殖系统在内的重要器官产生不利影响。Sudachitin (SCN) 是一种天然存在的类黄酮,具有广泛的生物潜力。本研究旨在探讨 SCN 对避免 PQ 诱导的大鼠睾丸毒性的缓解潜力。将 48 只雄性大鼠 (Rattus norvegicus) 分为 4 组,包括对照组、PQ (5 mg/kg + 30 mg/kg) 和 SCN (30 mg/kg) 仅治疗组。我们的研究结果表明,PQ 处理降低了核因子红细胞 2 相关因子 2 (Nrf-2) 及其抗氧化基因的表达,以及超氧化物歧化酶 (SOD) 、过氧化氢酶 (CAT)、谷胱甘肽还原酶 (GSR) 和谷胱甘肽过氧化物酶 (GPx) 的活性,同时提高了活性氧 (ROS) 和丙二醛 (MDA) 的水平。此外,PQ 中毒上调了 Keap-1 的表达,同时下调了 3-β 羟基类固醇脱氢酶 (3β-HSD)、17-β 羟基类固醇脱氢酶 (17β-HSD) 和类固醇生成急性调节蛋白 (StAR) 的表达。此外,暴露于 PQ 后精子异常增加。此外,PQ 暴露降低了血浆睾酮、黄体生成素 (LH) 和促卵泡激素 (FSH) 的水平,同时增加了白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、核因子-κ B (NF-κB)、白细胞介素-1β (IL-1β) 和环氧合酶-2 (COX-2) 的水平。此外,PQ 处理提高了半胱氨酰天冬氨酸特异性蛋白酶-3 (Caspase-3) 和 Bcl-2 相关 X 蛋白 (Bax) 的表达,同时下调了 B 细胞淋巴瘤-2 (Bcl-2) 的表达。 此外,PQ 暴露破坏了睾丸组织的正常结构。然而,SCN 治疗由于其抗氧化、抗炎和雄激素的潜力,通过调节上述破坏显着保护了睾丸组织。
更新日期:2024-08-24
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