Exercise, DNA damage and consideration for i) antioxidant supplementation in males and ii) female endocrinology

Abstract

Reactive oxygen and nitrogen species (RONS) are continuously produced in three main ways: (1) intercellularly as by-products of oxidative metabolism during the generation of ATP, (2) extracellularly and in a controlled manner via specialized enzymes as part of the evolutionary process of developing the innate immune system, and (3) exogenously, via exposure to external/environmental factors. On the one hand, at physiological levels, RONS act as key signalling molecules for normal cell function (i.e.,intracellular signalling, and immune function). On the other hand, in anoxidative stress state, whereby redox homeostasis is altered (excessive RONS production and impaired antioxidant systems), they can inevitably cause oxidative damage to DNA, lipids and proteins.

The experimental studies presented in this thesis investigated oxidative stress in both sexes, in response to strenuous aerobic exercise, with a particular focus on DNA damage in white blood cells. Furthermore, the use of an antioxidant effect was explored on the grounds of its effectiveness against exercise-induced oxidative stress and the DNA damage response. In study 1, the systematic review and meta-analysis (data from 35 studies), a significant increase in DNA damage was demonstrated immediately following an acute exercise bout, as well as following 4 hours and up to 1-day post-exercise, whereas this was not evident following 5-28 days

In study 2, twenty healthy males (33 ± 12 years) cycled at a medium exercise intensity (67 % of V̇O2max) for one hour. Results demonstrate an increase in DNA damage as a function of exercise (baseline vs. postexercise, P < 0.001), which decreased back to baseline levels following 3hours post-exercise. Furthermore, lipid hydroperoxides decreased as a function of exercise (baseline vs. 3 hours post-exercise, P < 0.05). Although 10g of ascorbic acid (AA) supplementation had no effect on DNA damage(time x group, P > 0.05), AA markedly increased ascorbyl free radical concentration following exercise (AA group; baseline vs post supplementation/post-exercise/3 hours post-exercise, P < 0.05).

In study 3, seven healthy females (35 ± 5 years) performed two bouts of treadmill exercise (average time 12 ± 2 mins) to exhaustion on day 26-28and 11-13 of their menstrual cycle corresponding to the late luteal phase (LL) and the late follicular phase (LF) (V̇O2max: 43.5 ± 5.9 and 42.3 ± 10.1mL kg− 1 min− 1, respectively). Results demonstrate no difference between phases (LF vs LL) or an interaction effect of time x phase (p > 0.05) but an increase in DNA damage as a function of exercise (pre-exercise vs postexercise, P < 0.05) by 357% and 200% in the LF and LL phases, respectively. Additionally, following exercise, lipid hydroperoxides increased by 10% (pre-exercise vs post-exercise, P < 0.05). There was no change in oestradiol concentration between phases and no antioxidant oestradiol effect on reducing DNA damage was observed (P > 0.05). Lastly, oestradiol was not correlated with DNA single strand breaks, but there was a positive strong correlation during the LL phase with DNA double strand breaks atbaseline (r = 0.79, P < 0.05).

In study 4, four healthy males (26 ± 2.6 years) performed a 1-hour steady state moderate-intensity treadmill run in either hypoxia or normoxia (FiO2= 0.16 and FiO2 = 0.21, respectively). Gene expression of GPx7 (associated with antioxidant capacity) was downregulated and NCF2 (associated with RONS production) was upregulated in both conditions (3 hours post-exercise vs baseline, P < 0.05). Results of these pilot data warrant further research regarding specific gene expression responses to hypoxic exercise.

In conclusion, medium and/or high-intensity aerobic exercise can induce temporal DNA damage which may underpin mechanisms of RONS/exercise mediated adaptation. The data demonstrates that, neither a chronic high ingested dose of AA in males nor the phase of the female menstrual cycle seem to affect or blunt this temporary observed exercise/DNA damage response

Date of Award	Dec 2024
Original language	English
Supervisor	Gareth Davison (Supervisor) & Conor McClean (Supervisor)