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


METHODS
Male 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.


RESULTS
Myricetin 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 regulators, in addition, AMP-activated protein kinase(AMPK) plays a crucial role in this process.


CONCLUSIONS
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.
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Dan
D
Zou
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Peng
P
Liu
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Ka
K
Chen
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Qi
Q
Xie
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Xinyu
X
Liang
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Qian
Q
Bai
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Qicheng
Q
Zhou
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Kai
K
Liu
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Ting
T
Zhang
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Jundong
J
Zhu
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University; Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Mantian
M
Mi
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D004272:DNA, Mitochondrial / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D001678:Organelle Biogenesis; D010805:Physical Conditioning, Animal; D020011:Protective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D005419:Flavonoids; D020011:Protective Agents; C040015:myricetin; D055372:AMP-Activated Protein Kinases