Vitamin U (Vit U) is a novel free‐radical scavenger. The protective effect of Vit U on valproic acid (VPA)‐induced lung damage was examined. Rats were divided into four groups: control rats; rats given Vit U (50 mg/kg/d, by gavage) for 15 days; rats treated with VPA (500 mg/kg/d, intraperitoneally) for 15 days; and rats were given VPA + Vit U (in same dose and time). On the 16th day of the experiment, the lungs were collected from rats. Lung structure, pulmonary oxidant/antioxidant parameters and Nrf2, α‐SMA, and collagen‐1 were evaluated by microscopic and biochemical analysis. Additionally, it was determined the interactions of Vit U with Nrf2 and Keap1 by in silico analysis. VPA administration increased lipid peroxidation and the activity of lactate dehydrogenase and myeloperoxidase. However, it decreased the glutathione level, and the activities of glutathione peroxidase, glutathione‐S‐transferase, catalase, and superoxide dismutase. VPA‐mediated oxidative stress prompted structural distortion and fibrotic alterations in the lung. Vit U supplementation reversed structural and biochemical alterations, induced antioxidant system through Nrf2 activation, and attenuated fibrosis by reducing collagen expression in VPA‐administered rats. However, Vit U pretreatment was unable to reduce α‐SMA levels in the lung of VPA‐treated rats. Molecular docking analysis showed the binding of Vit U to ETGE motif leads to dissociation of Nrf2 from the Nrf2/Keap1 complex and its transfer to nuclei. In conclusion, Vit U attenuated VPA‐induced tissue damage by restoring antioxidative systems through amelioration of Nrf2 activity in the lung under oxidative stress.

中文翻译：

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维生素U通过改善氧化应激对丙戊酸诱导的大鼠肺毒性的保护作用。

维生素U（Vit U）是一种新型的自由基清除剂。检查了Vit U对丙戊酸（VPA）诱导的肺损伤的保护作用。将大鼠分为四组：对照组；对照组。给予Vit U（50 mg / kg / d，灌胃）15天；用VPA（500 mg / kg / d，腹膜内）治疗15天的大鼠；给予大鼠VPA + Vit U（相同剂量和时间）。在实验的第16天，从大鼠收集肺。通过显微镜和生化分析评估了肺的结构，肺部氧化剂/抗氧化剂参数以及Nrf2，α-SMA和胶原蛋白-1。另外，通过计算机分析确定了Vit U与Nrf2和Keap1的相互作用。施用VPA可增加脂质过氧化作用以及乳酸脱氢酶和髓过氧化物酶的活性。但是，它降低了谷胱甘肽水平，S-转移酶，过氧化氢酶和超氧化物歧化酶。VPA介导的氧化应激促使肺部结构变形和纤维化改变。Vit U补充剂可逆转结构和生化改变，通过Nrf2激活诱导抗氧化系统，并通过降低VPA给药大鼠的胶原蛋白表达来减轻纤维化。但是，Vit U预处理无法降低VPA处理的大鼠肺中的α-SMA水平。分子对接分析表明，Vit U与ETGE基序的结合导致Nrf2从Nrf2 / Keap1复合物中解离，并转移到细胞核中。总之，Vit U通过改善氧化应激下肺中Nrf2的活性来恢复抗氧化系统，从而减轻了VPA诱导的组织损伤。