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膳食 NAC 减轻砷诱导的子宫卵巢功能障碍和凋亡基因表达的变化。

Mitigation of arsenic driven utero-ovarian malfunction and changes of apoptotic gene expression by dietary NAC.

机构信息

Department of Biomedical Laboratory Science and Management and Clinical Nutrition and Dietetics Division, Vidyasagar University, Midnapore, 721102, West Bengal, India.

Department of Biomedical Laboratory Science and Management and Clinical Nutrition and Dietetics Division, Vidyasagar University, Midnapore, 721102, West Bengal, India.

出版信息

Ecotoxicol Environ Saf. 2020 Aug;199:110675. doi: 10.1016/j.ecoenv.2020.110675. Epub 2020 May 8.

DOI:10.1016/j.ecoenv.2020.110675
PMID:32402895
Abstract

An oral painless dietary therapy is also indispensable in the management of arsenic toxicity despite of its conventional painful therapeutic management. The present study focused on the management of arsenic mediated female reproductive dysfunctions by dietary therapy of N-acetyl cysteine (NAC). Here, sodium arsenite was given at the dose of 10 mg/kg body weight orally for the first 8 day. Day 9 onwards up to day 16 these arsenicated rats were provided with NAC (250 mg/kg body weight) enriched basal diet once daily. Arsenic intoxicated group exhibited a comparable inactivation of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) due to oxidative stress in reproductive organs along with a simultaneous elevation of lipid peroxidation state and decline in non-protein soluble thiols (NPSH) level in female reproductive organs. Arsenic intoxication also accomplished with the up-regulation of inflammatory markers tumour necrosis factor (TNF α) and nuclear factor κB (NF κB). Pro-apoptotic Bax gene and p53 gene expressions were also raised due to arsenic intoxication while anti-apoptotic Bcl-2 gene expression was suppressed. In fact, arsenication decreased the circulating level of vitamin B and folic acid. Dietary NAC supplementation significantly reversed back the activity of antioxidant enzymes in arsenite fed rats towards normalcy and also sustained the normal reproductive cyclicity, utero-ovarian histo-morphology and estradiol receptor α (ER-α) expression in these reproductive organs. Dietary NAC exerted its positive action against arsenic intoxication by up-regulation of Bcl-2 gene expression along with the suppression of pro-apoptotic Bax gene and p53 gene. Thus, dietary NAC also plays anti-apoptotic, anti-inflammatory, and anti-oxidative role against arsenic toxicity. NAC also regulates the components (vitamin B and folic acid) of S-adenosylmethionine pool in the way of probable removal of arsenic from the system.

摘要

尽管砷中毒的传统治疗方法具有一定的疼痛性,但在管理过程中,口服无痛饮食疗法也是必不可少的。本研究专注于通过 N-乙酰半胱氨酸(NAC)的饮食疗法来治疗砷介导的女性生殖功能障碍。在这里,亚砷酸钠以 10mg/kg 体重的剂量口服给予 8 天。从第 9 天到第 16 天,这些砷化的大鼠每天给予富含 NAC(250mg/kg 体重)的基础饮食。由于生殖器官的氧化应激,砷中毒组的抗氧化酶超氧化物歧化酶(SOD)、过氧化氢酶和谷胱甘肽过氧化物酶(GPx)活性被类似地失活,同时生殖器官的脂质过氧化状态升高,非蛋白可溶性硫醇(NPSH)水平下降。砷中毒还伴随着炎症标志物肿瘤坏死因子(TNFα)和核因子κB(NFκB)的上调。由于砷中毒,促凋亡 Bax 基因和 p53 基因的表达也升高,而抗凋亡 Bcl-2 基因的表达受到抑制。事实上,砷化作用降低了循环维生素 B 和叶酸的水平。饮食 NAC 补充显著使亚砷酸盐喂养的大鼠的抗氧化酶活性恢复正常,并维持这些生殖器官的正常生殖周期性、子宫-卵巢组织形态和雌激素受体α(ER-α)表达。饮食 NAC 通过上调 Bcl-2 基因的表达,同时抑制促凋亡 Bax 基因和 p53 基因的表达,发挥其对砷中毒的积极作用。因此,饮食 NAC 还具有对抗砷毒性的抗凋亡、抗炎和抗氧化作用。NAC 还通过可能从系统中去除砷的方式调节 S-腺苷甲硫氨酸池的成分(维生素 B 和叶酸)。

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