The possible effects of baclofen on mitochondrial function

Mitochondria are critical organelles for energy production and cellular metabo-lism. Baclofen is widely used as a muscle relaxant in various medical fields and is particularly effective in the management of neurological disorders. This study investigated the potential effects of Baclofen on mitochondrial function due to its side effects such as muscle weakness, altered muscle tone and limited efficacy in treating movement disorders, which may indicate underlying mitochondrial dysfunction in patients with non-mitochondrial movement disorders. The main findings include: an increase in the mitochondrial integrated stress response (\($ISR^{mt}\)) in brain, kidney and skeletal muscle tissues; increased autophagy in brain tissue; increased mitochondrial biogenesis in kidney tissue; and a decrease in mitochondrial biogenesis in skeletal muscle. These changes suggest that Baclofen significantly affects tissue-specific mitochondrial responses. In the brain, increased (ISR^mt) and autophagy indicate strong cellular adaptations to stress conditions and this may affect neuroprotection and neural function. In the kidney, increased mitochondrial biogenesis and (ISR^mt) emphasize the role of Baclofen in regulating mitochondrial stress responses and promoting mitochondrial regeneration, which may affect renal energy metabolism. In contrast, reduced mitochondrial biogenesis in skeletal muscle indicates a negative effect on energy metabolism and muscle weakness as clinical signs. Furthermore, plasma analysis revealed a remarkable increase in circulating free mitochondrial DNA in Baclofen-treated animals, emphasising a systemic mitochondrial response. Despite the absence of significant phenotypic changes, the molecular changes observed provided insights into the complex effects of Baclofen on mitochondrial function and stress mechanisms and contributed to understanding its wider implications in cellular health and disease management.