Octreotide attenuates intestinal ischemia/reperfusion mischief in rats through modulation of Nrf2/PRX2/ASK1/JNK signaling pathway

Abstract

Intestinal ischemia/reperfusion (IIR) is a substantial cause of mortality and morbidity worldwide. Octreotide (OCT) has been proven to be effective against various organ insults. However, the exact mechanism by which it exerts protective effect against IIR is still obscure. Thus, the aim was to unveil the potential role of octreotide in an IIR model and decipher its mechanism of action. The rats were allocated into sham-operated, IIR, and OCT groups. Histopathological changes were performed to assess the intestinal injury. Immunohistochemical analysis was used to estimate the NF-κB, Bcl2, caspase-3, IL-17, LC3B, and beclin-1. The mRNA of TNF-α and IL-17 were examined using real time PCR. The levels of p-Nrf2, PRX2, p-JNK, ASK1, and LC3 were assessed using western blot technique. The levels of total antioxidant capacity and SOD were measured using appropriate kits. Furthermore, the protein expressions of Bax, caspase-3, ASK1, and Nrf2 were assessed using proper ELISA kits. Additionally, the comet assay was determined to investigate the effect on apoptosis. At the molecular level, OCT administration upregulated TAC and SOD levels, demonstrating its antioxidant effect. The anti-apoptotic effect was signified by the upregulation of Bcl2 and downregulation of Bax and caspase-3, which was confirmed by comet assay. Furthermore, OCT decreased the levels of TNF-α, NF-κB, and IL-17, confirming its anti-inflammatory effect. OCT pre-treatment triggered autophagy, as evidenced by the upregulation of beclin-1 and LC3B. These effects were accomplished by increasing p-Nrf2 and PRX2 and decreasing ASK1 and p-JNK. Consequently, this impeded the necrosis of intestinal cells and improved the intestinal histoarchitecture abnormalities. Ultimately, OCT successfully ameliorated IIR injury via modulating the Nrf2/PRX2/ASK1/JNK signaling trajectory, leading to autophagic, antioxidant, anti-apoptotic, and anti-inflammatory effects. Graphical abstract

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