Astaxanthin but not quercetin preserves mitochondrial integrity and function, ameliorates oxidative stress, and reduces heat‐induced skeletal muscle injury

Abstract

Heat stress causes mitochondrial dysfunction and increases mitochondrial production of reactive oxygen species (ROS), both of which contribute to heat‐induced skeletal muscle injury. In this study, we tested whether either astaxanthin or quercetin, two dietary antioxidants, could ameliorate heat‐induced skeletal muscle oxidative injury. In mouse C2C12 myoblasts exposed to 43°C heat stress, astaxanthin inhibited heat‐induced ROS production in a concentration‐dependent manner (1–20 μM), whereas the ROS levels remained high in cells treated with quercetin over a range of concentrations (2–100 µM). Because mitochondria are both the main source and a primary target of heat‐induced ROS, we then tested the effects of astaxanthin and quercetin on mitochondrial integrity and function, under both normal temperature (37°C) and heat stress conditions. Quercetin treatment at 37°C induced mitochondrial fragmentation and decreased membrane potential (ΔΨ m), accompanied by reduced protein expression of the master regulator of mitochondrial biogenesis peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α). It also induced cleavage of mitochondrial inner‐membrane fusion protein OPA1. In contrast, astaxanthin at 37°C increased protein expression of PGC‐1α and mitochondrial transcription factor A (TFAM), and maintained tubular structure and normal ΔΨm. Under 43°C heat stress conditions, whereas quercetin failed to rescue C2C12 cells from injury, astaxanthin treatment prevented heat‐induced mitochondrial fragmentation and depolarization, and apoptotic cell death. We also isolated rat flexor digitorum brevis myofibers and confirmed the data from C2C12 myoblasts that astaxanthin but not quercetin preserves mitochondrial integrity and function and ameliorates heat‐induced skeletal muscle injury. These results confirm that mitochondria may be a potential therapeutic target for heat‐related illness and suggest that astaxanthin may potentially be an effective preventive strategy.

Astaxanthin: A Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging

“…A fresh study showed that astaxanthin treatment helps to preserve mitochondrial integrity and function in heat-induced skeletal muscle injury examined in cultured C2C12 cells and isolated rat skeletal muscle fibers. The supplementation prevented mitochondrial fragmentation and depolarization, reduced apoptotic cell death, and increased PGC-1 α and mitochondrial transcription factor A expression following heat stress [119]. Human investigations have also been carried out to show the effect of astaxanthin application on exercise-induced muscle injury.…”

Astaxanthin alleviates spinal cord ischemia-reperfusion injury via activation of PI3K/Akt/GSK-3β pathway in rats

“…Besides, AST has a therapeutic role in preserving cognitive function by promoting or maintaining neural plasticity in aged patients and in neurodegenerative disease [ 30 ]. It has also been shown to maintain mitochondrial integrity and function and ameliorate oxidative stress in skeletal muscle injury [ 31 ]. Recent studies that reported AST shows prominent antioxidant and/or anti-inflammatory properties in different models of ischemia and reperfusion injury confirmed its protective action, such as in steatotic liver, muscle, and brain tissue [ 18 , 32 – 34 ].…”

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

“…It is conceivable from the literature presented in this review that AX is a very unique compound that prevents the structural destruction of proteins and lipids in mitochondria associated with highly reactive ROS-induced peroxidation reactions, such as hydroxyl radicals, lipid free radicals, and singlet oxygen, without affecting mitochondria-derived superoxide or H 2 O 2 signaling. There is an interesting report that proves this concept: a comparison of mitochondrial function during heat stress using a skeletal muscle cell model between quercetin under heat stress [ 238 ]. Quercetin is a well-known polyphenolic compound which has antioxidant activity and promotes mitochondria biogenesis via the AMPK/PGC-1 pathway, as well as AX [ 239 , 240 , 241 , 242 ].…”