Protective effects of myricetin on acute hypoxia-induced exercise intolerance and mitochondrial impairments in rats.

Dan Zou,Xinyu Liang,Ting Zhang,Ka Chen,Kai Liu,Qi Xie,Qian Bai,Qicheng Zhou,Jundong Zhu,Mantian Mi,Peng Liu,Stephen E Alway

doi:10.1371/journal.pone.0124727

Abstract

PurposeExercise tolerance is impaired in hypoxia. The aim of this study was to evaluate the effects of myricetin, a dietary flavonoid compound widely found in fruits and vegetables, on acute hypoxia-induced exercise intolerance in vivo and in vitro.MethodsMale rats were administered myricetin or vehicle for 7 days and subsequently spent 24 hours at a barometric pressure equivalent to 5000 m. Exercise capacity was then assessed through the run-to-fatigue procedure, and mitochondrial morphology in skeletal muscle cells was observed by transmission electron microscopy (TEM). The enzymatic activities of electron transfer complexes were analyzed using an enzyme-linked immuno-sorbent assay (ELISA). mtDNA was quantified by real-time-PCR. Mitochondrial membrane potential was measured by JC-1 staining. Protein expression was detected through western blotting, immunohistochemistry, and immunofluorescence.ResultsMyricetin supplementation significantly prevented the decline of run-to-fatigue time of rats in hypoxia, and attenuated acute hypoxia-induced mitochondrial impairment in skeletal muscle cells in vivo and in vitro by maintaining mitochondrial structure, mtDNA content, mitochondrial membrane potential, and activities of the respiratory chain complexes. Further studies showed that myricetin maintained mitochondrial biogenesis in skeletal muscle cells under hypoxic conditions by up-regulating the expressions of mitochondrial biogenesis-related regluators, in addition, AMP-activated protein kinase(AMPK) plays a crucial role in this process.ConclusionsMyricetin may have important applications for improving physical performance under hypoxic environment, which may be attributed to the protective effect against mitochondrial impairment by maintaining mitochondrial biogenesis.

Highlights

Mitochondria are the major site of cellular energy production in the form of ATP in mammalian cells[1], and skeletal muscle mitochondrial content is an important determinant of endurance capacity[2]
Further studies showed that myricetin maintained mitochondrial biogenesis in skeletal muscle cells under hypoxic conditions by up-regulating the expressions of mitochondrial biogenesisrelated regluators, in addition, AMP-activated protein kinase(AMPK) plays a crucial role in this process
Myricetin may have important applications for improving physical performance under hypoxic environment, which may be attributed to the protective effect against mitochondrial impairment by maintaining mitochondrial biogenesis

Summary

Introduction

Mitochondria are the major site of cellular energy production in the form of ATP in mammalian cells[1], and skeletal muscle mitochondrial content is an important determinant of endurance capacity[2]. Previous studies have demonstrated that acute and severe hypobaric hypoxia could increase oxidative stress and impair mitochondrial function in skeletal muscle[3, 4]. Given that mitochondrial dysfunction was an important limiting factor for exercise capacity under hypoxic conditions, strategies to prevent mitochondrial impairment and promote mitochondrial repair are predicted to improve exercise performance in hypoxia. Despite the potential significance of mitochondrial function improvement by maintaining mitochondrial biogenesis in hypoxia-induced exercise intolerance, few strategies to protect mitochondrial biogenesis have been studied to increase exercise tolerance under hypoxic conditions

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