Oxidative Stress-Mediated Skeletal Muscle Degeneration: Molecules, Mechanisms, and Therapies

Table 1

Pharmacological compounds used for antioxidant therapies in muscle degenerative disorders.

Compound	Predicted mode of action	Preclinical trial (mdx mouse)	Clinical trial
ACE inhibitors	Inhibits proinflammatory and prooxidant activity of Angiotensin II	Improved muscle function; enhanced resistance to exercise-induced muscle necrosis; reduced ROS production; reduced NF-B activity [105]
AICAR	AMPK agonist; activates autophagy-mitophagy pathway	Improvement in diaphragm histopathology and force generation; normalized mitochondria calcium sensitivity [64]
Creatine	Downstream product of glycine and arginine amino acids; quenches aqueous ROS	Improved muscle function; restored mitochondrial respiration capacity [122]	4-month administration to 30 DMD patients yielded significantly improved muscle function [123, 124]
Curcumin	Curcuminoid from turmeric; NF-κB inhibitor	Improved sarcolemma integrity and muscle force; reduced TNF-α and iNOS levels [101]
Deferoxamine	Iron-chelating agent	Reduced muscle damage and inflammatory response; reduced 4-hydroxynoneal and dihydroethidium staining [102]
Epigallocatechin gallate	Polyphenol antioxidant compound from green tea extract	Improved muscle histology and physiology; reduced lipofuscin granules in diaphragm muscle; increased utrophin expression [106, 107]
Idebenone	Short-chain analogue of Coenzyme Q; improves mitochondrial ETC function with antioxidant properties	Improved cardiac and running performance; reduction in inflammation and fibrosis [113]	52-week treatment on 31 DMD patients significantly improved respiratory function, albeit its efficacy is more prominent in patients who have not previously undergone steroid-treatment [112, 114]
IRFI-042	Synthetic vitamin E analogue; NF-κB inhibitor	Partial restoration of limb strength and fatigue level; reduced oxidative stress; diminished NF-κB-induced TNF-α expression [53]
Melatonin	Endogenous ROS and RNS scavenger	Improved muscle function; reduced creatine kinase level; improved redox status of muscle [108]	3-month administration significantly reduced creatine kinase level, lipid peroxidation, nitrites, and NF-κB-mediated inflammatory cascade; reduced hyperoxidative status of erythrocytes [109, 110]
N-acetylcysteine	Cysteine precursor; thiol-containing scavenger	Prevented exercise-induced muscle necrosis and elevation of creatine kinase level; reduced glutathione and protein thiol oxidation [31, 54]
Nifedipine	Calcium channel blocker	Improved muscle function; enhanced resistance to exercise-induced muscle necrosis; reduction of iNOS and NADPH mRNA expression [104]
Pentoxifylline	Phosphodiesterase inhibitor	Restored muscle strength; enhanced resistance to exercise-induced muscle necrosis; reduced creatine kinase level and ROS production [97]	12-month administration to 64 DMD patients produced no significant difference compared to the placebo group [98]
Rapamycin nanoparticles	mTORC1 inhibitor; activates autophagy	Increased skeletal muscle strength and cardiac contractile performance in both mdx and aged wild-type muscle [115–117]
Resveratrol	Polyphenol in grapes and wine; SIRT1 activator	Improved muscle mass; reduced fibroblast infiltration; reduced nitrotyrosine [119]