INVESTIGATING THE ROLE OF DJ-1 AND NRF2 IN MANAGING RENAL ISCHEMIA-REPERFUSION INJURY: IMPLICATIONS FOR ATHLETE HEALTH IN DIABETIC CONDITIONS

Abstract

This study investigates the role of DJ-1 and NRF2 in mediating renal ischemia-reperfusion injury (IRI), a condition that may also impact athletes, especially those with underlying diabetic conditions, during high-intensity physical activities. Utilizing thirty-two rats, models of diabetic nephropathy (DR) and renal IRI were established and treated with t-BHQ, a NRF2 activator, and ML285, a NRF2 inhibitor. The findings indicated that ischemia-reperfusion significantly exacerbated renal damage, as evidenced by worsened histological scores and increased oxidative stress in diabetic rats. Treatment with t-BHQ mitigated these effects, reducing renal injury and oxidative stress markers. Conversely, inhibition of NRF2 via ML285 reversed the protective effects of t-BHQ, underscoring the pivotal role of NRF2 in guarding against renal damage. Notably, both DJ-1 and NRF2 protein levels were elevated in response to t-BHQ treatment, while ML285 treatment reduced their expression. Additionally, caspase-3, a marker of cellular apoptosis, was upregulated in response to IRI, t-BHQ, and ML285 treatments. These results suggest that the modulation of NRF2 by DJ-1 could be a promising therapeutic target for preventing IRI, particularly in athletes who are at increased risk due to strenuous activities and underlying diabetic conditions. This study highlights potential molecular targets for enhancing renal resilience in athletes, providing insights into new mechanisms for preventing acute kidney injuries in high-stress scenarios.