Transfluthrin: A household insecticide alters glucose metabolism, mitochondrial function and induces atrophy in C2C12...

Non-communicable diseases (NCDs) are increasing globally. Numerous studies have associated pesticide exposure with metabolic alterations in skeletal muscle and the development of related NCDs. Transfluthrin (TF), a volatile type-I pyrethroid insecticide, is widely used as a household mosquito repellent. Although effective in preventing mosquito-borne diseases, recent in vitro and in vivo studies have implicated it in oxidative stress and genotoxic effects. However, its effects on skeletal muscle remain poorly characterized. This study investigated the dose-dependent subtoxic effects of TF on skeletal muscle cell integrity using C2C12 myotubes. Subtoxic concentrations (10 µM, 25 µM, and 50 µM) were selected via MTT assay, and cultured myotubes were exposed to TF for 24 h. Along with altered morphology, TF-treated myotubes showed a dose-dependent increase in glucose consumption and uptake. TF disrupted glucose metabolism, as evidenced by reduced glycogen storage and elevated lactate production. In addition, mitochondrial dysfunction was confirmed by decreased MTT reduction, reduced succinate dehydrogenase activity, and membrane depolarization. TF induced oxidative stress, reflected by increased reactive oxygen species (ROS) lipid peroxidation (LPO), and catalase activity, along with reduced glutathione (GSH) levels in treated myotubes. Immunostaining further revealed myotube atrophy in TF-treated myotubes, associated with increased calpain activity and MuRF-1 protein expression. This study demonstrates, for the first time, that TF directly impairs skeletal muscle cell metabolism by inducing oxidative stress, mitochondrial dysfunction, atrophy, and altered glucose utilization, highlighting under-recognized health risks associated with excessive routine household insecticide exposure.