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.
Subject(s)
Anesthetics/pharmacology , Colon/drug effects , Consciousness/drug effects , Ethanol/analogs & derivatives , NF-E2-Related Factor 2/metabolism , Anesthesia Recovery Period , Anesthetics/toxicity , Animals , Collagen/metabolism , Colon/metabolism , Colon/pathology , Ethanol/pharmacology , Ethanol/toxicity , Female , Fibrosis , Inflammation Mediators/metabolism , Mice, Inbred C57BL , Mice, Knockout , NF-E2-Related Factor 2/deficiency , NF-E2-Related Factor 2/genetics , Oxidative Stress/drug effects , Time FactorsABSTRACT
The authors examined a group of 160 persons employed at an exposure to small concentration (below HAC) of nitrogen and ammonia oxides, and a group of 130 controls. It was found that in the group of subjects exposed to toxic compounds the percentage of persons suffering from inflammation of the upper respiratory tract was much higher (37.5%) than in the control group (13.1%). Olfactometric examinations indicated a disadvantageous effect of the mentioned compounds upon the acuity of the sense of smell, whereas rhinospirometric examination did not reveal any differences between the control group and the group of persons exposed to nitrogen and ammonia oxides.