关键词: apoptosis naringin oxidative stress paclitaxel testicular toxicology

Mesh : Animals Male Oxidative Stress / drug effects Testis / drug effects metabolism pathology Rats Flavanones / pharmacology Paclitaxel / toxicity adverse effects Apoptosis / drug effects MAP Kinase Signaling System / drug effects Rats, Sprague-Dawley Cytokines / metabolism Antioxidants / pharmacology

来  源:   DOI:10.1002/jbt.23751

Abstract:
Paclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX-induced testicular toxicity. Thirty-five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX-induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1 beta, cyclooxygenase-2, interleukin-6, inducible-nitric oxide synthase, mitogen-activated protein kinase 14 (MAPK)14, MAPK15, c-Jun N-terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO-1, NQO1 and Bcl-2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX-induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX-induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy.
摘要:
紫杉醇(PTX),它被积极地用于治疗许多类型的癌症,通过引起睾丸组织氧化应激增加而产生毒性作用。柚皮苷(NRG)是一种在植物中发现的天然类黄酮,它的抗氧化性能处于最前沿。本研究旨在探讨NRG在PTX致睾丸毒性中的保护作用。将35只雄性SD大鼠分为5组:对照组,NRG,PTX,PTX+NRG50和PTX+NRG100。大鼠服用PTX(2mg/kg,BW)腹膜内,每天一次,持续第5天。然后,在第6天到第14天之间,每天一次口服施用NRG(50和100mg/kg)。NRG减少了PTX诱导的脂质过氧化并增加了睾丸组织的抗氧化能力(超氧化物歧化酶,过氧化氢酶,谷胱甘肽过氧化物酶,和谷胱甘肽)。而NRG降低了核因子κB的mRNA表达水平,肿瘤坏死因子-α,白细胞介素-1β,环氧合酶-2,白细胞介素-6,诱导型一氧化氮合酶,丝裂原活化蛋白激酶14(MAPK)14,MAPK15,c-Jun氨基末端激酶,睾丸组织中P53,Apaf1,Caspase3,Caspase6,Caspase9和Bax;它引起Nrf2,HO-1,NQO1和Bcl-2水平的增加。NRG还改善了被PTX破坏的睾丸组织的结构和功能完整性。NRG减轻了PTX诱导的精子损伤。NRG通过增加氧化应激减轻PTX诱导的睾丸毒性表现出保护作用,炎症,凋亡,和自噬。
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