Oxidative Stress in Rat Testis and Epididymis Under Intermittent Hypobaric Hypoxia: Protective Role of Ascorbate Supplementation

Abstract

Hypobaric hypoxia (HH), an environmental condition of high altitude encountered by mountaineers, miners, and observatory, rural health, border patrol, and rural education workers, jeopardizes normal physiologic functions in humans. The present study was conducted to evaluate the effects of intermittent HH (IHH; equivalent to 4600 m above mean sea level) on oxidative stress and the protective role of dietary ascorbic acid on rat testis and epididymis. Ten-week-old male Wistar rats were assigned to 1 of 6 groups: 1) normobaric (Nx), 2) Nx + physiologic solution (Nx + PS), 3) Nx + ascorbic acid (Nx + AA), 4) IHH, 5) IHH + PS, or 6) IHH + AA. Animals subjected to IHH were exposed for 96 hours followed by normobaric conditions for 96 hours for a total of 32 days. The control groups (2 and 5) were injected with doses of PS, and the treated groups (3 and 6) were injected with doses of AA (10 mg 6kg 21 body weight) at an interval of 96 hours. Rats were sacrificed on day 32 after initiation of the protocol. The testis and epididymis were collected to determine the activity and expression of glutathione reductase and the levels of lipid peroxide formation. An epididymal sperm count was also performed in each animal. The results of this study revealed that IHH induced lipid peroxidation, a reduction in glutathione reductase activity in testis and epididymis, and a significant decrease in epididymal sperm count. Treatment with AA prevented these changes. In conclusion, AA was capable of decreasing oxidative stress in testis and epididymis under IHH. This protection by AA of the IHH-induced lipid peroxidation can be explained in part by the preservation of glutathione reductase activity in these organs.

Pharmacological approaches in either intermittent or permanent hypoxia: A tale of two exposures

“…Recent studies reinforce the existence of an increased oxidative metabolism in rat epididymis subjected to ICH [45,46]. Hence, an increased production of ROS gives way to a rise in apoptosis at the germinal cell level, leading to a state of hypospermatogenesis [46,47].…”

“…One potential alternative is to incorporate food with high antioxidant levels to the diet in those people exposed to HA, and we have shown that this may have a positive effect in the protection of cells facing oxidative stress [45]. We described, in rats exposed to ICH, that testicles and epididymis shown an increase in lipid peroxidation markers and lower GSH levels compared with normoxic normobaric animals, and that these effects were fully reverted with concomitant administration of ascorbic acid, blueberry extracts or Ω3 chronic supplementation [44,45,46]. Indeed, these protective effects can be supported by the induction of enzymatic and non-enzymatic antioxidant defense systems.…”

Reversible Effect of High Altitude on Rat Testis Morphology and Spermatogenesis: Histological and Ultrastructural Study

“…Furthermore, the study avails ready information on the effects addressed in the different areas of altitude in the Kingdom of Saudi Arabia. Most investigations were carried out in high altitude laboratories or hypobaric chambers and did not simulate natural conditions (Saxena, 1995;Farias et al, 2010). The current study is again unique, as it addresses the effect of natural hypoxia on the morphology of rats exposed to natural areas of HA and then LA in the same country.…”

Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia

“…Chronic and IHH have been associated with increased oxidative damage in the testis [6]. IHH induces high levels of lipid peroxidation, reduces glutathione reductase activity, and decreases the epididymal sperm count [7]. This environment causes more severe damage in reproductive function to immigrants than natives.…”