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

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.

• Authors: Yilin Wang, Jin Wen, Marwan Almoiliqy, Yaojia Wang, Zhihao Liu, Xiaobo Yang, Xiaolong Lu, Qiang Meng, Jinyong Peng, Yuan Lin, Pengyuan Sun
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 5147069 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34630849 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Yilin Wang et al.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Dioxoles
• Lignans
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Plant Extracts
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, rat
• sesamin

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Antioxidants (administration & dosage)
• Apoptosis (drug effects)
• Cell Line
• Dioxoles (administration & dosage)
• Disease Models, Animal
• Epithelial Cells (drug effects, metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• Intestinal Diseases (drug therapy, metabolism)
• Intestinal Mucosa (cytology)
• Lignans (administration & dosage)
• Male
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Oxidative Stress (drug effects)
• Phytotherapy (methods)
• Plant Extracts (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism)
• Sesamum (chemistry)
• Signal Transduction (drug effects, genetics)
• Transfection
• Treatment Outcome