2. Academic Validation
  3. Nicotinamide adenine dinucleotide phosphate alleviates intestinal ischemia/reperfusion injury via Nrf2/HO-1 pathway

Nicotinamide adenine dinucleotide phosphate alleviates intestinal ischemia/reperfusion injury via Nrf2/HO-1 pathway

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113478. doi: 10.1016/j.intimp.2024.113478.
Su-Ying Chen 1,  Hui Xu 2,  Yan Qin 3,  Tian-Qi He 4,  Rui-Rui Shi 5,  Yu-Run Xing 6,  Jian Xu 4,  Ruo-Chen Cong 7,  Mei-Rong Wang 7,  Ju-Shun Yang 7,  Jin-Hua Gu 8,  Bo-Sheng He 9
Affiliations

Affiliations

  • 1 Department of Radiology, Affiliated Hospital 2 of Nantong University, Medical School of Nantong University, Nantong 226001, China; Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China; Department of Ultrasonography, Wuxi City Rehabilitation Hospital, Liangxi District Chinese Medicine Hospital, Wuxi 214000, China.
  • 2 Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China. Electronic address: xuhui@ntu.edu.cn.
  • 3 Department of Pharmacy, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China.
  • 4 Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China; Department of Pharmacy, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China.
  • 5 Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China.
  • 6 Department of Radiology, Affiliated Hospital 2 of Nantong University, Medical School of Nantong University, Nantong 226001, China; Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China.
  • 7 Department of Radiology, Affiliated Hospital 2 of Nantong University, Medical School of Nantong University, Nantong 226001, China.
  • 8 Nantong Institute of Genetics and Reproductive Medicine, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China; Department of Pharmacy, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong 226001, China. Electronic address: jhgu@ntu.edu.cn.
  • 9 Department of Radiology, Affiliated Hospital 2 of Nantong University, Medical School of Nantong University, Nantong 226001, China; Translational Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, China. Electronic address: 15906290998@163.com.
PMID: 39471691 DOI: 10.1016/j.intimp.2024.113478
Abstract

Intestinal ischemia-reperfusion (I/R) injury is a critical condition in the abdomen that has significant morbidity and fatality rates. Prior studies have noted the defensive role of the coenzymatic antioxidant reduced nicotinamide adenine dinucleotide phosphate (NADPH) in heart and brain I/R damage, yet its impact on intestinal I/R trauma required further exploration. Through the application of an in vitro oxygen-glucose deprivation-reoxygenation model and a mouse model of short-term intestinal I/R, this study clarified the defensive mechanisms of NADPH against intestinal I/R injury. We demonstrated that intraperitoneal NADPH administration markedly reduced interleukin-1β (IL-1β) levels and blocked NLRP3 inflammasome activation, hence reducing inflammation. The antioxidative properties of NADPH were established by the reduction of oxidative stress markers and enhancement of glutathione levels. Importantly, NADPH improved intestinal barrier integrity, indicated by an upregulation of zonula occludens-1 and the promotion of a balanced gut microbiome profile. Furthermore, we identified the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathway as a crucial conduit for NADPH's beneficence. When this pathway was inhibited by ML385, the favorable outcomes conferred by NADPH were significantly abrogated. These results demonstrate that NADPH functions as an antioxidative, anti-inflammatory, microbiota-balancing, barrier-strengthening, and anti-inflammatory agent against intestinal I/R damage through activation of the Nrf2/HO-1 signaling pathway.

Keywords

Inflammation; Intestinal I/R injury; Intestinal flora; NADPH; Nrf2/HO-1; Oxidative stress.

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