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Research has suggested that the HO\u2013CO pathway imparts protective effects to hypoxic tissues. The objective of this study was to investigate the effects of acute (4\u2005h or 24\u2005h at 7% O2) and chronic (7\u2005days at 11% O2) hypoxia on the HO\u2013CO pathway in the hypoxia-tolerant naked mole-rat. Specifically, we measured CO concentrations in nine organs and blood, as well as HO activity in all organs of animals exposed to normoxia (21% O2), acute hypoxia or chronic hypoxia. Hypoxia did not impact CO concentration or HO activity in most tissues, with the exception of the brain (decreased [CO] after 24\u2005h and 7\u2005days), heart (increased HO activity after 4\u2005h), and intestine (increased [CO] after 24\u2005h and 7\u2005days but decreased HO activity after 24\u2005h). Relative to normoxic controls, hemoglobin concentrations increased 10\u201312% in animals exposed to acute hypoxia but were unchanged following chronic hypoxia. In naked mole-rats exposed to normoxia or hypoxia, CO concentrations were higher in blood, lung and spleen, and HO activity was higher in the kidney and lung when compared with tissues from mice exposed to normoxia. However, splenic HO activity was higher in mice exposed to normoxia when compared with spleen from naked mole-rats in all treatment conditions. Unlike non-hypoxia tolerant species, chronic hypoxia did not suppress the HO\u2013CO pathway in naked mole-rats, highlighting the importance of this pathway in hypoxia physiology.<\/jats:p>","DOI":"10.1242\/jeb.250502","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T08:28:11Z","timestamp":1762763291000},"source":"Crossref","is-referenced-by-count":1,"title":["Impact of acute and chronic hypoxia on the heme oxygenase\/carbon monoxide pathway in naked mole-rats (\n                    <i>Heterocephalus glaber<\/i>\n                    )"],"prefix":"10.1242","volume":"228","author":[{"given":"Kristi M.","family":"Kezar","sequence":"first","affiliation":[{"name":"University of North Carolina Wilmington 1 Department of Biology and Marine Biology , , Wilmington, NC 28403 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Eaton","sequence":"additional","affiliation":[{"name":"University of Ottawa 2 Department of Biology , , Ottawa, ON , K1N 9A7","place":["Canada"]},{"name":"Ottawa Institute of Systems Biology, University of Ottawa 3 , Ottawa, ON , K1H 8M5","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Kadamani","sequence":"additional","affiliation":[{"name":"University of Ottawa 2 Department of Biology , , Ottawa, ON , K1N 9A7","place":["Canada"]},{"name":"Ottawa Institute of Systems Biology, University of Ottawa 3 , Ottawa, ON , K1H 8M5","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Ojaghi","sequence":"additional","affiliation":[{"name":"University of Ottawa 2 Department of Biology , , Ottawa, ON , K1N 9A7","place":["Canada"]},{"name":"Ottawa Institute of Systems Biology, University of Ottawa 3 , Ottawa, ON , K1H 8M5","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo E.","family":"Otterbein","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Center for Life Sciences, Harvard Medical School 4 Division of Gastroenterology, Hepatology and Transplantation , , Boston, MA 02215 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew E.","family":"Pamenter","sequence":"additional","affiliation":[{"name":"University of Ottawa 2 Department of Biology , , Ottawa, ON , K1N 9A7","place":["Canada"]},{"name":"Ottawa Institute of Systems Biology, University of Ottawa 3 , Ottawa, ON , K1H 8M5","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-0509","authenticated-orcid":false,"given":"Michael S.","family":"Tift","sequence":"additional","affiliation":[{"name":"University of North Carolina Wilmington 1 Department of Biology and Marine Biology , , Wilmington, NC 28403 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"2025121207033422300_JEB250502C1","doi-asserted-by":"publisher","first-page":"F1137","DOI":"10.1152\/ajprenal.90449.2008","article-title":"Heme oxygenase: the key to renal function regulation","volume":"297","author":"Abraham","year":"2009","journal-title":"Am. 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