First Author | Kopacz A | Year | 2020 |
Journal | Biomed Pharmacother | Volume | 128 |
Pages | 110317 | PubMed ID | 32485566 |
Mgi Jnum | J:321331 | Mgi Id | MGI:6820114 |
Doi | 10.1016/j.biopha.2020.110317 | Citation | Kopacz A, et al. (2020) Nrf2 transcriptional activity in the mouse affects the physiological response to tribromoethanol. Biomed Pharmacother 128:110317 |
abstractText | 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. |