Chemical Inhibition of NRF2 Transcriptional Activity Influences Colon Function and Oestrogen Receptor Expression in Mice at Different Ages

Abstract

We aim to investigate whether chemical inhibition of NRF2 transcriptional activity (TA) influences distal colon contractions, particularly in an age-dependent manner in females, and whether it impacts oestrogen receptor signalling in female mice. This study was performed on 3 and 6-month-old female mice treated with ML385 (30 mg/kg) or a vehicle for 7 days (i.p.). The colon functionality was verified with a colon bead expulsion test; serum samples were collected for oestradiol levels, and colon samples were stored for various histological analyses. The results show that the seven-day treatment of ML385 significantly downregulated TA (p < 0.05) and impacted its contractility. Additionally, young females treated with ML385 exhibited an increase in goblet cell number and significantly increased ERα, but not ERβ, especially in older mice. It is worth noting that the basal level of the membrane oestrogen receptor GPR30 was higher in older mice within the epithelial layer, and ML385 treatment led to a downregulation of GPR30 in 6-month-old mice. In summary, ML385 decreases NRF2 TA in the colon and impacts its contractility and goblet cell numbers. Additionally, NRF2 TA influences the expression of oestrogen receptors in the colons of female mice.