Sensitivity to Oxidative Stress: Sex Matters

The excessive production of free radicals in organism and the imbalance between the concentration of these and the antioxidant defences has been related to the process of aging. It has been postulated that oxidative processes and antioxidant defence can bee sex related. Besides, we have noticed that at old age 60% of male mice developed hepatocellular tumors which were absent in females. Thus, it is of interest to determine oxidative and antioxidative status of aging male and female mice under conventional oxygen conditions and in 100-percet oxygen with possible mechanisms involved. The process of lipid peroxidation and antioxidant enzyme activity was age and sex-related, favouring males over females throughout the lifespan. The sensitivity of a cell to free radical attack apparently depends on the relationship among antioxidant enzymes rather than on absolute activities of individual antioxidant enzymes. Indeed, our results imply stronger correlative links in old female than male mice, which might explain why old females are better protected from oxidative stress than males. In the liver of hyperoxia treated mice sex-related difference was found at the physiological level observing malondialdehyde (MDA) increment (one of the end products of lipid peroxidation) and increased catalase (CAT) activity only in male mice. Hyperoxia did upregulate a stress responsive enzyme heme-oxygenase-1 (HO-1), but only in female mice. Also, stress related izoenzymes of the cytochrome P450 family were changed. In female mice Cyp1A1 and Cyp1A2 were downregulated and Cyp2A5 was upregulated. The results of our study suggest that females are less susceptible to oxidative stress by two major mechanisms: upregulated expression of HO-1 genes and different expression of certain P450 enzymes.