Naked mole-rats are among the few mammals with the ability to endure severe
hypoxia. These unique rodents use metabolic rate depression along with various molecular mechanisms to successfully overcome the challenges of
oxygen-limitation, which they experience in their underground borrows. While studies have reported that naked mole-rats exhibit inherently higher levels of oxidative damage across their lifespan as compared to mice, it has yet to be determined whether naked mole-rats are vulnerable to oxidative damage during periods of low
oxygen exposure. To investigate this phenomenon, we examined cellular oxidative damage markers of macromolecules:
DNA oxidation determined as 8-oxo-2'deoxyguanosine (8-OHdG8) levels,
RNA oxidation as
8-hydroxyguanosine (8-OHG), protein carbonylation, and lipid peroxidation in normoxic (control), acute (4 h at 7% O2), and chronic (24 h at 7% O2)
hypoxia-exposed naked mole-rats. Brain appears to be the most resilient to
hypoxia-induced oxidative damage, with both brain and heart exhibiting enhanced
antioxidant capacity during
hypoxia. Levels of
DNA and
RNA oxidation were minimally changed in all tissues and no changes were observed in protein carbonylation. Most tissues experienced lipid peroxidation, with liver displaying a 9.6-fold increase during
hypoxia. Concomitantly, levels of DNA damage repair
proteins were dynamically regulated in a tissue-specific manner, with white adipose displaying a significant reduction during
hypoxia. Our findings show that naked mole-rats largely avoid
hypoxia-induced oxidative damage, possibly due to their high tolerance to redox stress, or to reduced oxidative requirements made possible during their hypometabolic response when
oxygen supply is limited.