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柚皮素通过调节 Nrf-2/Keap-1、炎症、甾体生成和组织学特征缓解百草枯诱导的雄性大鼠睾丸毒性。

Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf-2/Keap-1, Inflammatory, Steroidogenic, and Histological Profile.

机构信息

Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan.

Department of Zoology, Govt. College Women University, Sialkot, Pakistan.

出版信息

Environ Toxicol. 2024 Dec;39(12):5284-5295. doi: 10.1002/tox.24408. Epub 2024 Aug 23.

DOI:10.1002/tox.24408
PMID:39179512
Abstract

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.

摘要

百草枯(PQ)是一种有毒的除草剂,会对包括男性生殖系统在内的重要器官造成不良影响。地榆素(SCN)是一种天然存在的类黄酮,具有广泛的生物学潜力。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)分为四组,包括对照组、PQ(5mg/kg)组、PQ+SCN(5mg/kg+30mg/kg)组和仅 SCN(30mg/kg)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,同时升高了活性氧(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 羟甾脱氢酶(3β-HSD)、17-β 羟甾脱氢酶(17β-HSD)和甾体急性调节蛋白(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)和卵泡刺激素(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-κB(NF-κB)、白细胞介素-1β(IL-1β)和环加氧酶-2(COX-2)的水平。此外,PQ 处理上调了半胱天冬氨酸特异性蛋白酶-3(Caspase-3)和 B 细胞淋巴瘤-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 治疗通过调节上述破坏显著保护睾丸组织,这归因于其抗氧化、抗炎和雄激素潜力。

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