[Direct mechanism of action in toxic myopathies]

Toxic myopathies are a large group of disorders generated by surrounding agents and characterized by structural and/or functional disturbances of muscles. The most recurrent are those induced by commonly used medications. Illicit drugs, environmental toxins from animals, vegetables, or produced by micro-organisms as well as chemical products commonly used are significant causes of such disorders. The muscle toxicity results from multiple mechanisms at different biological levels. Many agents can induce myotoxicity through a direct mechanism in which statins, glucocorticoids and ethyl alcohol are the most representative. Diverse mechanisms were highlighted as interaction with macromolecules and induction of metabolic and cellular dysfunctions. Muscle damage can be related to amphiphilic properties of some drugs (chloroquine, hydroxychloroquine, etc.) leading to specific lysosomal disruptions and autophagic dysfunctions. Some agents affect the whole muscle fiber by inducing oxidative stress (ethyl alcohol and some statins) or triggering cell death pathways (apoptosis or necrosis) resulting in extensive alterations. More studies on these mechanisms are needed. They would allow a better knowledge of the intracellular mediators involved in these pathologies in order to develop targeted therapies of high efficiency.