New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju 61005, Korea.
Cells. 2021 Apr 26;10(5):1017. doi: 10.3390/cells10051017.
Inflammation-mediated skeletal muscle wasting occurs in patients with sepsis and cancer cachexia. Both conditions severely affect patient morbidity and mortality. Lithium chloride has previously been shown to enhance myogenesis and prevent certain forms of muscular dystrophy. However, to our knowledge, the effect of lithium chloride treatment on sepsis-induced muscle atrophy and cancer cachexia has not yet been investigated. In this study, we aimed to examine the effects of lithium chloride using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell-conditioned media, maintained the expression of the muscle fiber contractile protein, myosin heavy chain 2, and inhibited the upregulation of the E3 ubiquitin ligase, Atrogin-1. In addition, it inhibited the upregulation of inflammation-associated cytokines in macrophages treated with lipopolysaccharide. In the animal model of sepsis, lithium chloride treatment improved body weight, increased muscle mass, preserved the survival of larger fibers, and decreased the expression of muscle-wasting effector genes. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength, and increased fiber cross-sectional area, with no significant effect on tumor mass. These results indicate that lithium chloride exerts therapeutic effects on inflammation-mediated skeletal muscle wasting, such as sepsis-induced muscle atrophy and cancer cachexia.
炎症介导的骨骼肌消耗发生在脓毒症和癌症恶病质患者中。这两种情况都严重影响了患者的发病率和死亡率。氯化锂先前已被证明可增强成肌作用并预防某些形式的肌肉营养不良。然而，据我们所知，氯化锂治疗对脓毒症引起的肌肉萎缩和癌症恶病质的影响尚未得到研究。在这项研究中，我们旨在使用癌症恶病质和脓毒症的体外和体内模型来检验氯化锂的作用。氯化锂可防止在含有癌细胞条件培养基培养的肌管中发生消耗，维持肌肉纤维收缩蛋白肌球蛋白重链 2 的表达，并抑制 E3 泛素连接酶 Atrogin-1 的上调。此外，它可抑制脂多糖处理的巨噬细胞中与炎症相关的细胞因子的上调。在脓毒症动物模型中，氯化锂治疗可改善体重，增加肌肉量，保存较大纤维的存活，并降低肌肉消耗效应基因的表达。在癌症恶病质模型中，氯化锂增加了肌肉量，增强了肌肉力量，并增加了纤维横截面积，而对肿瘤质量没有明显影响。这些结果表明，氯化锂对炎症介导的骨骼肌消耗具有治疗作用，例如脓毒症引起的肌肉萎缩和癌症恶病质。
