Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO-1/NQO1 Signaling Pathway

• Published in: Oxidative medicine and cellular longevity 2021, Vol.2021 (1), p.5147069-5147069
• Main Authors: Wang, Yilin, Wen, Jin, Almoiliqy, Marwan, Wang, Yaojia, Liu, Zhihao, Yang, Xiaobo, Lu, Xiaolong, Meng, Qiang, Peng, Jinyong, Lin, Yuan, Sun, Pengyuan
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Antioxidants - administration & dosage; Apoptosis; Apoptosis - drug effects; Cell Line; Cytokines; Dioxoles - administration & dosage; Disease Models, Animal; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Experiments; Heme Oxygenase (Decyclizing) - metabolism; Hypoxia; Injuries; Intestinal Diseases - drug therapy; Intestinal Diseases - metabolism; Intestinal Mucosa - cytology; Ischemia; Laboratory animals; Lignans - administration & dosage; Male; Medical research; Microscopy; Morphology; NAD(P)H Dehydrogenase (Quinone) - metabolism; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Oxidative Stress - drug effects; Phytotherapy - methods; Plant Extracts - administration & dosage; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Sesamum - chemistry; Signal Transduction - drug effects; Signal Transduction - genetics; Small intestine; Transfection; Treatment Outcome; Tumor necrosis factor-TNF
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2021/5147069

Intestinal ischemia-reperfusion (I/R) may induce cell/tissue injuries, leading to multiple organ failure. Based on our preexperiments, we proposed that sesamin could protect against and ameliorate intestinal I/R injuries and related disorders with involvement of activating Nrf2 signaling pathway. This proposal was evaluated using SD intestinal I/R injury rats in vivo and hypoxia/reoxygenation- (H/R-) injured rat small intestinal crypt epithelial cell line (IEC-6 cells) in vitro. Sesamin significantly alleviated I/R-induced intestinal histopathological injuries and significantly reduced serum biochemical indicators ALT and AST, alleviating I/R-induced intestinal injury in rats. Sesamin also significantly reversed I/R-increased TNF-α, IL-6, IL-1β, and MPO activity in serum and MDA in tissues and I/R-decreased GSH in tissues and SOD in both tissues and IEC-6 cells, indicating its anti-inflammatory and antioxidative stress effects. Further, sesamin significantly decreased TUNEL-positive cells, downregulated the increased Bax and caspase-3 protein expression, upregulated the decreased protein expression of Bcl-2 in I/R-injured intestinal tissues, and significantly reversed H/R-reduced IEC-6 cell viability as well as reduced the number of apoptotic cells among H/R-injured IEC-6 cell, showing antiapoptotic effects. Activation of Nrf2 is known to ameliorate tissue/cell injuries. Consistent with sesamin-induced ameliorations of both intestinal I/R injuries and H/R injuries, transfection of Nrf2 cDNA significantly upregulated the expression of Nrf2, HO-1, and NQO1, respectively. On the contrary, either Nrf2 inhibitor (ML385) or Nrf2 siRNA transfection significantly decreased the expression of these proteins. Our results suggest that activation of the Nrf2/HO-1/NQO1 signaling pathway is involved in sesamin-induced anti-inflammatory, antioxidative, and antiapoptotic effects in protection against and amelioration of intestinal I/R injuries.