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-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.
Highlights
Intestinal ischemia-reperfusion (I/R) can be caused by acute mesenteric ischemia, severe infection, traumatic shock, and surgical procedures, leading to multiple organ dysfunction and systemic inflammatory response syndrome [1, 2]
Several mechanisms are involved in intestinal I/R injury, such as microvascular dysfunction [35], excessive production of reactive oxygen species [36,37,38], inflammation [39,40,41], and cell apoptosis [42,43,44]
The increase of serum aminotransferase levels, such as AST and ALT, caused by remote organ injuries is one of the characteristics of intestinal I/R injury [28, 46, 47]. Proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), IL-6, and IL-1β, in serum of intestinal I/R animals are significantly increased [22, 28, 48], which is related to neutrophil activation and tissue damage caused by I/R [47, 49]
Summary
Intestinal ischemia-reperfusion (I/R) can be caused by acute mesenteric ischemia, severe infection, traumatic shock, and surgical procedures, leading to multiple organ dysfunction and systemic inflammatory response syndrome [1, 2]. Intestinal I/R injuries still represent a great challenge in clinical practice, with high morbidity and mortality [3]. Sesamin (Figure 1), a natural lignin compound, is isolated from sesame seeds, and it possesses health beneficial effects, including anti-inflammatory, anticancer, antihypertensive, antithrombotic, antidiabetic, antiatherogenic, antiobesity, and Oxidative Medicine and Cellular Longevity O H H. CAS name: Sesamin CAS registry number: 607-80-7 IUPAC name: 5-[(3S,3aR,6S,6aR)-3-(1,3benzodioxol-5-yl)-1,3,3a,4,6,6a-exahydrofuro[3,4c]furan-6-yl]-1,3-benzodioxole Molecular formula: C20H18O6 Molecular mass: 354.35 Melting point: 124 oC Physical description: Solid [Sesamin. CAS, a division of the American Chemical Society, n.d. https://commonchemistry.cas.org/detail?cas_rn=60780-7 (retrieved 2021-08-03) (CAS RN: 607-80-7).
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