Nrf2 transcriptional activity in the mouse affects the physiological response to tribromoethanol - 18/06/20
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Highlights |
• | tNrf2-/-mice respond to Avertin with prolonged anaesthesia and recovery time. |
• | Avertin impairs colon morphology in Nrf2+/+ but not in tNrf2-/- mice. |
• | Colon morphology changes in tNrf2-/- are associated with altered collagens level. |
• | Enhanced oxidative stress or inflammation was not observed in colon of tNrf2-/-. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : 2,2,2-tribromoethanol, Nrf2, Anaesthesia, Toxicity, Inflammation, Collagens
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