Unraveling the protective mechanisms of Angiotensin-(1–7) in Intestinal Ischemia-Reperfusion injury: Interplay between Nrf-2/HO-1 and NF-κB/NLRP3 pathways

AIM: Intestinal ischemic reperfusion (I-I/R) injury is a serious clinical case with high death rate. This research assessed the influence of Angiotensin 1-7 (Ang-(1-7)) alone on the induced I-I/R injury or combined with each of nuclear factor erythroid 2 related factor 2 (Nrf-2) inhibitor (ML-385) or Mas receptor antagonist (A779). The primary objective of our study was to assess the role of Mas receptor and Nrf-2 pathway in mediating the probable protective effect of Ang-(1-7) against intestinal I/R injury. MATERIAL AND METHODS: Albino rats from Wistar strain were separated into; Sham group, I-I/R group, I-I/R+ Ang-(1-7), I-I/R+ Ang-(1-7)+ A779 and I-I/R+ Ang-(1-7)+ ML-385. Serum C reactive protein level (CRP) and markers of intestinal barrier malfunction were assessed. Measurements of the intestinal levels of Ang-(1-7), Angiotensin II (Ang II), angiotensin converting enzyme 2 (ACE2), in addition to the markers of oxidation, inflammation and apoptosis were taken. Also, Gene expression of heme oxygenase-1 (HO-1), Western blotting test of NOD-like receptor protein 3 (NLRP3) and immunoexpression of Nrf-2 and nuclear factor kappa B P56 (NF-κB P65) were assessed in the intestinal tissues. KEY FINDINGS: Ang-(1-7) secured against I-I/R injury through its suppressive action on oxidative stress, inflammation and apoptosis, but this protective effect was completely blocked with Mas receptor blocker and partially blocked with Nrf-2 inhibitor. SIGNIFICANCE: Ang-(1-7)/Mas receptors axis gave its protective influence via augmenting Nrf-2/HO-1 pathway and attenuating NF-κB/NLRP3 inflammasome pathway.