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Nrf2 transcriptional activity in the mouse affects the physiological response to tribromoethanol.
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2020-05-30 , DOI: 10.1016/j.biopha.2020.110317
A Kopacz 1 , E Werner 2 , D Kloska 1 , K Hajduk 1 , J Fichna 3 , A Jozkowicz 1 , A Piechota-Polanczyk 1
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Up to date, there is no information on the influence of 2,2,2-tribromoethanol (TBE; Avertin), a commonly used anaesthetic, on mice with impaired antioxidant capacity. We aimed to analyse the effect of a single dose of Avertin on anaesthesia duration time, inflammatory response, oxidative stress and collagen deposition in the large intestine of Nrf2 transcriptional knockout mice (tNrf2−/−). The studies were performed on six-month-old female mice Nrf2+/+ and tNrf2−/− randomly assigned to Avertin (250 mg/kg b.w. single i.p. injection) or vehicle group. We observed a 2-fold increase in anaesthesia time and longer recovery time (p = 0.015) in tNrf2−/− in comparison to Nrf2+/+. However, no hepato- or nephrotoxicity was detected. Interestingly, we found severe changes in colon morphology of untreated tNrf2-/- mice associated with colon shortening (p = 0.02) and thickening (p = 0.015). Avertin treatment caused colon damage manifested with epithelial layer damage and goblet depletion in Nrf2+/+ mice but not in tNrf2−/− individuals. Additionally, Avertin did not induce oxidative stress in colon tissue, but it increased leukocyte infiltration in Nrf2+/+ mice (p = 0.02). Immunofluorescent staining also revealed enhanced deposition of collagen I and collagen III in the colon of untreated tNrf2−/− mice. Avertin contributed to increased deposition of collagen I in Nrf2+/+ mice but reduced deposition of collagen I and III in tNrf2−/− individuals. In conclusion, tNrf2−/− respond to Avertin with prolonged anaesthesia that is not associated with acute toxicity, inflammatory reaction or enhanced oxidative stress. Avertin does not impair intestine morphology in tNrf2−/− mice but can normalise the enhanced fibrosis.



中文翻译:

小鼠中的Nrf2转录活性影响对三溴乙醇的生理反应。

迄今为止,尚无关于常用的麻醉剂2,2,2-三溴乙醇(TBE; Avertin)对抗氧化能力受损的小鼠的影响的信息。我们旨在分析单剂量的Avertin对Nrf2转录敲除小鼠(tNrf2 -/-)大肠内麻醉持续时间,炎症反应,氧化应激和胶原沉积的影响。该研究在六个月大的雌性小鼠Nrf2 + / +和tNrf2 -/-上随机分配给Avertin(250 mg / kg bw单次ip注射)或媒介物组进行。与Nrf2 + / +相比,我们观察到tNrf2 -/-的麻醉时间增加了2倍,恢复时间更长(p = 0.015)。但是,未检测到肝毒性或肾毒性。有趣的是,我们发现未经治疗的tNrf2 -/-小鼠结肠形态发生了严重变化,与结肠缩短(p = 0.02)和增厚(p = 0.015)有关。在Nrf2 + / +小鼠中,Avertin治疗引起的结肠损伤表现为上皮层损伤和杯状细胞耗竭,而在tNrf2 -/-个体中则没有。此外,Avertin不会在结肠组织中诱发氧化应激,但会增加Nrf2 + / +小鼠中的白细胞浸润(p = 0.02)。免疫荧光染色还显示,未经处理的tNrf2 -/-小鼠结肠中胶原蛋白I和胶原蛋白III的沉积增强。Avertin促进Nrf2 + / +中胶原蛋白I的沉积小鼠,但减少了tNrf2 -/-个体中的胶原蛋白I和III的沉积。总之,tNrf2 -/-对Avertin的反应时间长,与急性毒性,炎症反应或氧化应激增加无关。Avertin不会损害tNrf2 -/-小鼠的肠道形态,但可以使增强的纤维化正常化。

更新日期:2020-05-30
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