AEROBIC EXERCISE MITIGATES DEXAMETHASONE INDUCED CARDIAC OXIDATIVE STRESS VIA MODULATION OF NADPH OXIDASE

Author(s): HAYTA, U., OZEKLIG, B., GUNGOR-ORHAN, I., DEMIREL, A.H., ONBASILAR, I., AKIN, Y., GURAY, U., DEMIRKAN, B., AKIN, S., Institution: UNIVERSITY OF WÜRZBURG, Country: GERMANY, Abstract-ID: 548

INTRODUCTION:
Chronic or high-dose glucocorticoids can elevate cardiac oxidative damage [1], promoting oxidative myocardial injury and adverse cardiac remodelling, in part via NADPH oxidases (NOX2 and NOX4) [2,3]. Exercise is known to enhance endogenous antioxidant defenses4. This study examined whether aerobic exercise attenuates dexamethasone‑induced oxidative stress in rat myocardium [4].
METHODS:
Male Wistar Albino rats were randomized to Control (C, n=8), Dexamethasone (D, n=8), or Dexamethasone+Exercise (DE, n=8). D and DE received subcutaneous dexamethasone (1 mg·kg⁻¹·day⁻¹) for 21 days; DE completed treadmill running (25 m·min⁻¹, 60 min/day, 5 days/week). Controls received volume‑matched saline. Left ventricular NOX2, NOX4, p22phox, Nrf2, and 4‑hydroxynonenal (4‑HNE) were quantified by Western blot; advanced oxidation protein products (AOPP), superoxide dismutase (SOD), and catalase (CAT) were measured spectrophotometrically.
RESULTS:
Dexamethasone increased 4‑HNE in D and DE (p<0.0001, p<0.05), and exercise attenuated this rise in DE (p<0.05). AOPP increased in D versus C (p<0.01); DE differed from D (p<0.01) but not from C (p>0.05). SOD activity rose in both D and DE, whereas CAT increased only in DE (p<0.05). Nrf2 increased in D (p<0.0001), whereas no change was observed in DE (p>0.05). NOX2 increased in both GC-treated groups, while NOX4 and p22phox increased only in D; p22phox was lower in DE than in D (p<0.05) and did not differ from C (p>0.05).
CONCLUSION:
Aerobic exercise mitigates GC‑induced cardiac oxidative stress by modulating NADPH oxidase components and augmenting antioxidant responses, supporting exercise as a non‑pharmacological cardioprotective strategy during GC exposure.
Refrence
1- Hayta U, Akin S, Gungor I, Colluoglu IT, Guray U, Akin Y, Demirel HA. Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production. Cardiovasc Drugs Ther. 2025 Feb;39(1):165-169.
2- Kracun D et al. NADPH oxidases and HIF1 in glucocorticoid excess. Redox Biol. 2020.
3- Lassègue B, San Martín A, Griendling KK. NADPH oxidases in the cardiovascular system. Circ Res. 2012.
4- Powers SK, Sollanek KJ, Wiggs MP, Demirel HA, Smuder AJ. Exercise-induced improvements in myocardial antioxidant capacity: the antioxidant players and cardioprotection. Free Radic Res. 2014 Jan;48(1):43-51.