The response of peroxiredoxins to hypoxia/reoxygenation stress induced in primary cultured fibroblasts from aquatic mammals

Aquatic mammals, such as Cetaceans (whales and dolphins) and Pinnipeds (seals and sea lions), are a group of mammals that have adapted to life in aquatic environments, including some remarkable deep-diving species. Efficient management of oxygen (O 2 ) consumption is crucial, as the rate of O 2 use increases with the duration of the dive, eventually leading to hypoxia. To counter this, physiological adaptations like bradycardia and vasoconstriction help ensure that vital organs receive sufficient oxygen during dives. However, these adjustments result in reduced blood flow to other tissues, potentially leading to ischemia/reperfusion injury caused by reactive oxygen species (ROS). Interestingly, despite these conditions, oxidative damage is not observed in aquatic mammals. In this case, we aimed to investigate how peroxiredoxins (PRDX), an enzymatic antioxidant responsible for H2O2 removal, respond to hypoxia/reoxygenation in primary cultured fibroblasts from different species of aquatic animals and terrestrial species. We performed CellROX staining to confirm that our cells are generating ROS and qPCR to measure the gene expression of all PRDX isoforms (1-6) in each treatment. Our results showed a higher production of ROS in short reoxygenation exposure (5 min) for all species with a decrease in long exposure (30 minutes), suggesting that cells rapidly produce ROS following hypoxia, with a decrease over time. PRDX1 was identified as the most highly expressed isoform in most species. Additionally, certain species showed distinct isoform expression patterns, such as elevated PRDX2 in the pygmy sperm whale compared to the dolphin and cow and PRDX3 in the northern elephant seal when compared to sea lion and dog. We conclude that aquatic mammals produce ROS in hypoxia/reoxygenation and peroxiredoxins respond to this oxidative stress state with a species-specific pattern, helping the cells avoid oxidative damage. São Paulo Research Foundation and UC Berkeley This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.