Protective Role And Potential Mechanism Of Quercetin Against Intense Exercise-induced Myocardium And Liver Damage

Objective:1. To investigate the protection of quercetin against intense exercise-induced oxidative stress focused on myocardium and liver.2. To investigate the protective effect of quercetin on intense exercise-induced oxidative stress and dysfunction focused on myocardial mitochondria.3. To evaluate whether overexpression of inflammatory mediators induced in the liver by intense exercise could be prevented by quercetin and whether the protective effect of quercetin was related with inhibition of NF-κB activation.Methods:All adult male mice were randomly divided into six groups of eight animals each:rested controls (Ct), intense exercise (Ex), Ex+dietary quercetin20mg/(kg·d)(Ex+Qu20), Ex+dietary quercetin50mg/(kg-d)(Ex+Qu50), Ex+dietary quercetin100mg/(kg-d)(Ex+Qu100) and rested plus dietary quercetin supplementation (Qu). Quercetin was administrated for4weeks and intense exercise program was performed as described by Marra with some modifications at the fourth week. Simply, the mice were acclimated to running on a motor-driven treadmill for2successive days, beginning at10m/min on a5°slope for10min/day, and then submitted to daily sessions of intense exercise for7consecutive days following a two-day rest. Mice were run at28m/min on a5°slope for90min while a10-min warm-up was maintained. Immediately upon final exercise, the mice were sacrificed. Results:1. Compared to normal control mice, Qu100treatment decreased intense exercise-induced the leakage of creatine kinase-MB (P<0.01), aspartate aminotransferase (P<0.01), and alanine aminotransferase (P<0.01). Intense exercise resulted in sustained oxidative stress and ultrastructural malformation on myocardium and liver which was evidently reversed by quercetin intervention.2. Quercetin pretreatment partially normalized intense exercise-induced myocardial mitochondrial oxidative stress and decline of mitochondrial membrane potential (P<0.01) and respiratory control ratio (RCR)(P<0.01).3. Significant increases postexercise were measured for serum TNF-a (P<0.01), IL-1β (P<0.01), IL-6(P<0.01), and IL-10(P<0.05) levels compared with normal control mice, quercetin pretreatment to exercise mice substantially decreased TNF-a (P<0.05), IL-1β (P<0.05), and IL-6(P<0.05) levels but not IL-10.4. Compared to normal control mice, exercise coursed with a significant rise in hepatic IL-1β (P<0.01), IL-6(P<0.01), and IL-10(P<0.01) mRNA levels. These effects of IL-1β (P<0.05) and IL-6(P<0.01) were significantly reduced by quercetin.5. Compared to normal control mice, intense exercise resulted in a significant increase of hepatic iNOS (P<0.01), COX-2(P<0.01), and ICAM-1(P<0.01) mRNA levels by3.2fold,1.6fold and0.7fold, respectively, and iNOS (P<0.01), COX-2(P<0.05), and ICAM-1(P<0.05) mRNA levels were partially blocked by quercetin administration compared with exercised mice. Intense exercise increased hepatic protein levels of iNOS, COX-2and ICAM-1which were evidently reversed by quercetin intervention.6. Following acute exercise, NF-κB was evident and colocalized with many of the nuclei. Comprared with exercised mice, quercetin pretreatment partially reduced the transfer of NF-κB into the nuclei. 7. Intense exercise resulted in a significant decrease of the nonphosphorylated form (-0.59fold)(P<0.05), while phosphorylated IkBα protein level was markedly increased (+1.7fold) compared with normal control (P<0.01). These effects were partially blocked by quercetin prevention (P<0.05). Protein level of P-IKKa was up-regulated in exercised mice (+9.9fold)(P<0.01), and this effect was obviously suppressed by quercetin intervention (P<0.01).8. Compared to normal control mice, intense exercise induced a marked activation of NF-κB (115%)(P<0.01) that was evidently blocked in liver of animals treated with quercetin (P<0.01).Conclusion:1. Quercetin exhibited protective role on intense exercise-induced oxidative stress injuries of myocardium and liver.2. Quercetin may protect mouse myocardium from intense exercise injury, including ultrastructural damage and mitochondrial dysfunction, through its antioxidative effect on mitochondria.3. Quercetin protects mouse liver against intense exercise damage, and impaired production of noxious mediators involved in P-IKKα/IκBα/P-IκBα inflammatory process and down-regulation of the NF-κB signal transduction pathway appear to contribute to the beneficial anti-inflammatory effects of quercetin.