Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Consortium for Health and Military Performance, Department of Military and Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Life Sci. 2022 Jan 1;288:120160. doi: 10.1016/j.lfs.2021.120160. Epub 2021 Nov 18.
This study aimed to: 1) investigate sex differences in heat-induced mitochondrial dysfunction, ROS production, and skeletal muscle injury in mice; 2) evaluate whether curcumin and astaxanthin, alone or together, would prevent those heat-induced changes.
Male and female C57BL/6J mice were treated with curcumin and astaxanthin for 10 days, then exposed to 39.5 °C heat for up to 3 h. Heat-induced hyperthermia, changes in mitochondrial morphology and function, and oxidative damage to skeletal muscle were evaluated.
Although female mice had a slightly higher basal core body temperature (Tc) than male mice, peak Tc during heat exposure was significantly lower in females than in males. Heat increased ROS levels in skeletal muscle in both sexes; interestingly, the increases in ROS were greater in females than in males. Despite the above-mentioned differences, heat induced similar levels of mitochondrial fragmentation and membrane potential depolarization, caspase 3/7 activation, and injury in male and female skeletal muscle. Individual treatment of curcumin or astaxanthin did not affect basal and peak Tc but prevented heat-induced mitochondrial dysfunction, ROS increases, and apoptosis in a dose-dependent manner. Moreover, a low-dose combination of curcumin and astaxanthin, which individually showed no effect, reduced the heat-induced oxidative damage to skeletal muscle.
Both male and female mice can develop mitochondrial dysfunction and oxidative stress in skeletal muscle when exposed to heat stress. High doses of either curcumin or astaxanthin limit heat-induced skeletal muscle injury, but a low-dose combination of these ingredients may increase their efficacy.
本研究旨在：1）研究热诱导的线粒体功能障碍、ROS 产生和骨骼肌损伤在雄性和雌性小鼠中的性别差异；2）评估姜黄素和虾青素单独或联合使用是否可以预防这些热诱导的变化。
雄性和雌性 C57BL/6J 小鼠用姜黄素和虾青素处理 10 天，然后暴露于 39.5°C 的热环境中长达 3 小时。评估热诱导的体温过高、线粒体形态和功能的变化以及骨骼肌的氧化损伤。
尽管雌性小鼠的基础核心体温（Tc）略高于雄性小鼠，但在热暴露期间，雌性小鼠的峰值 Tc 明显低于雄性小鼠。热应激增加了两性骨骼肌中的 ROS 水平；有趣的是，ROS 的增加在雌性中比在雄性中更为显著。尽管存在上述差异，但热应激在雄性和雌性骨骼肌中诱导了相似水平的线粒体碎片化和膜电位去极化、半胱天冬酶 3/7 激活和损伤。姜黄素或虾青素的单独治疗并不影响基础和峰值 Tc，但以剂量依赖性方式预防热诱导的线粒体功能障碍、ROS 增加和细胞凋亡。此外，姜黄素和虾青素的低剂量组合，单独使用时没有效果，可降低热应激对骨骼肌的氧化损伤。
雄性和雌性小鼠在暴露于热应激时均可发生线粒体功能障碍和骨骼肌氧化应激。高剂量的姜黄素或虾青素可限制热诱导的骨骼肌损伤，但这些成分的低剂量组合可能会提高其疗效。
