Abstract
The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+ restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.
Highlights
Moderate exercise provides benefits to health, weight, and mood management
There were no significant differences in the initial body weights among the 4 experimental groups
The results of this study demonstrate the beneficial effects of quercetin on liver damage following exhaustive exercise
Summary
Accumulating evidence has demonstrated that regular physical activity enhances the antioxidant and anti-inflammatory properties and functional capacities of various tissues and organs. These factors minimize or prevent chronic problems, including the common nonalcoholic fatty liver disease [1]. Injury and dysfunction of the liver, a vital organ responsible for the metabolism of nutrients and biochemical, inflammatory mediators and Oxidative Medicine and Cellular Longevity the detoxification of toxic substances, were first reported by Fojt et al [4]. In contrast with the widely studied exercise-induced heart injury models [8], studies of liver damage have drawn little attention due to the lack of evident clinical symptoms in early stages. To prevent progression to advanced and fatal liver damage and to develop early intervention strategies, it is imperative to explore the molecular mechanisms underlying liver damage especially on endoplasmic reticulum stress (ERS) and inflammation induced by overexercise
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