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Impact of acute and chronic hypoxia on the heme oxygenase/carbon monoxide pathway in naked mole-rats (Heterocephalus glaber)

K. Kezar,Liam Eaton,Karen L Kadamani,Mohammad Ojaghi,Leo E. Otterbein,M. Pamenter,M. S. Tift

Published 2025 in Journal of Experimental Biology

ABSTRACT

ABSTRACT Heme oxygenase (HO) enzymes are responsible for the degradation of free heme and producing endogenous carbon monoxide (CO). Research has suggested that the HO–CO pathway imparts protective effects to hypoxic tissues. The objective of this study was to investigate the effects of acute (4 h or 24 h at 7% O2) and chronic (7 days at 11% O2) hypoxia on the HO–CO 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 h and 7 days), heart (increased HO activity after 4 h), and intestine (increased [CO] after 24 h and 7 days but decreased HO activity after 24 h). Relative to normoxic controls, hemoglobin concentrations increased 10–12% 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–CO pathway in naked mole-rats, highlighting the importance of this pathway in hypoxia physiology.

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