Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO‐1/NQO1 Signaling Pathway
Yilin Wang, Jin Wen, Marwan Almoiliqy, Yaojia Wang, Zhihao Liu, Xiaobo Yang, Xiao‐Long Lu, Qiang Meng, Jinyong Peng, Yuan Lin, Pengyuan Sun
Abstract
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‐1 β , 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.