Nrf2 transcriptional activity in the mouse affects the physiological response to tribromoethanol

by Selleckchem | Apr 26 2023

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.

Comments：

It seems that your study aimed to investigate the effects of 2,2,2-tribromoethanol (TBE; Avertin) on mice with impaired antioxidant capacity. Here is a summary of your findings:

A single dose of Avertin (250 mg/kg b.w. single i.p. injection) caused a 2-fold increase in anaesthesia time and longer recovery time in tNrf2-/- mice compared to Nrf2+/+ mice.
Avertin did not cause hepato- or nephrotoxicity in either tNrf2-/- or Nrf2+/+ mice.
Untreated tNrf2-/- mice showed severe changes in colon morphology, including colon shortening and thickening, as well as enhanced deposition of collagen I and collagen III in the colon.
Avertin caused colon damage manifested with epithelial layer damage and goblet depletion in Nrf2+/+ mice but not in tNrf2-/- individuals.
Avertin did not induce oxidative stress in colon tissue, but it increased leukocyte infiltration in Nrf2+/+ mice.
Avertin contributed to increased deposition of collagen I in Nrf2+/+ mice but reduced deposition of collagen I and III in tNrf2-/- individuals.
Based on these findings, it appears that tNrf2-/- mice respond to Avertin with prolonged anaesthesia without acute toxicity, inflammatory reaction, or enhanced oxidative stress. Avertin does not impair intestine morphology in tNrf2-/- mice but can normalize the enhanced fibrosis. These results suggest that Nrf2 deficiency may affect the response to Avertin anesthesia and should be taken into account in future studies.