Role and Potential Mechanism of Heme Oxygenase-1 in Intestinal Ischemia-Reperfusion Injury

• Prif Awduron: Kazuhiro Katada (Awdur), Tomohisa Takagi (Awdur), Takaya Iida (Awdur), Tomohiro Ueda (Awdur), Katsura Mizushima (Awdur), Akifumi Fukui (Awdur), Tetsuya Okayama (Awdur), Kazuhiro Kamada (Awdur), Kazuhiko Uchiyama (Awdur), Takeshi Ishikawa (Awdur), Yuji Naito (Awdur), Yoshito Itoh (Awdur)
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• Cyhoeddwyd: MDPI AG, 2022-03-01T00:00:00Z.
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Intestinal ischemia-reperfusion (IR) injury is a complex, multifactorial, and pathophysiological condition with high morbidity and mortality, leading to serious difficulties in treatment, especially in humans. Heme oxygenase (HO) is the rate-limiting enzyme involved in heme catabolism. HO-1 (an inducible form) confers cytoprotection by inhibiting inflammation and oxidation. Furthermore, nuclear factor-erythroid 2-related factor 2 (Nrf2) positively regulates HO-1 transcription, whereas BTB and CNC homolog 1 (Bach1) competes with Nrf2 and represses its transcription. We investigated the role and potential mechanism of action of HO-1 in intestinal IR injury. Intestinal ischemia was induced for 45 min followed by 4 h of reperfusion in wild-type, Bach1-deficient, and Nrf2-deficient mice, and a carbon monoxide (CO)-releasing molecule (CORM)-3 was administered. An increase in inflammatory marker levels, nuclear factor-κB (NF-κB) activation, and morphological impairments were observed in the IR-induced intestines of wild-type mice. These inflammatory changes were significantly attenuated in Bach1-deficient mice or those treated with CORM-3, and significantly exacerbated in Nrf2-deficient mice. Treatment with an HO-1 inhibitor reversed this attenuation in IR-induced Bach1-deficient mice. Bach1 deficiency and treatment with CORM-3 resulted in the downregulation of NF-κB activation and suppression of adhesion molecules. Together, Bach1, Nrf2, and CO are valuable therapeutic targets for intestinal IR injury.

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10.3390/antiox11030559
2076-3921