Dependence of Antioxidant and Transcriptional Responses to Periodic Hypoxia on Sex and Age in Rats

Biochemistry (Mosc). 2026 May;91(5):816-835. doi: 10.1134/S0006297926600249.

ABSTRACT

Periodic hypoxia is a condition characterized by alternating episodes of oxygen deprivation (hypoxia) and periods of normal or elevated oxygen levels (reoxygenation). Depending on severity and duration of exposure, periodic hypoxia can activate both protective and pathological mechanisms. The aim of this study was to evaluate dependence of the effects of acute and periodic hypoxia on sex and age of rats. Male and female Wistar rats aged 2 and 4 months were used. The animals were exposed to normobaric hypoxia (8% O₂, 2 h) either once or daily for 5 consecutive days. Subsequently, changes in body weight, activity and content of antioxidant system enzymes in blood plasma, as well as expression levels of the HIF-1α, GPx4, BDNF, and caspase-3 genes in the frontal cortex, hippocampus, and striatum of the brain were assessed. It was shown that daily hypoxia exposure leads to the decrease in body weight in both male and female rats of both ages. In the males, age-dependent changes in activity of antioxidant enzymes and increased expression of hypoxia marker genes in the brain were observed after a single hypoxia exposure. After multiple exposures, the recorded parameters did not differ from the control values. In the females, exposure to hypoxia did not affect activity of antioxidant enzymes, and increase in the expression of the studied genes was observed only after five daily exposures to hypoxia. The experiments revealed significant differences in the response to acute and periodic hypoxia exposure between male and female rats. These data should be considered when developing experimental models of periodic hypoxia and studying the mechanisms of adaptive and pathological reactions of the body to repeated hypoxia/reoxygenation episodes.

PMID:42219392 | DOI:10.1134/S0006297926600249