Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway
Katila, N. et al. (2021) Metformin attenuates rotenone-induced oxidative stress and mitochondrial damage via the AKT/Nrf2 pathway. Neurochem. Intl. 148, 105120. DOI: 10.1016/j.neuint.2021.105120
Rotenone, a broad-spectrum insecticide and piscicide, is often used in animal models to induce pathological characteristics of Parkinson’s disease (PD). Previously, the antidiabetic drug metformin has shown neuroprotective effects against rotenone-induced dopaminergic neuronal loss in PD models. Multiple mechanisms of action have been studied for these effects; however, little is known about metformin-induced attenuation of oxidative stress in neurons.
This study examined the antioxidative and mitochondrion-protective properties of metformin. The researchers treated human neuroblastoma cells (SH-SY5Y) with various concentrations of rotenone to determine the optimal cytotoxic dose. To assess the neuroprotective effect of metformin, they pretreated cells with varying concentrations of metformin. Metformin showed neuroprotective activity and significantly reduced rotenone-induced caspase 3/7 activation. Further, this activity of metformin appeared to be dependent on the 5′ adenosine monophosphate-activated protein kinase (AMPK) pathway.
The researchers also showed that metformin aided in restoration of mitochondrial function after rotenone-induced toxicity, as well as reducing cytosolic and mitochondrial levels of reactive oxygen species (ROS). They linked the restorative effects of metformin to upregulation of transcription factor Nrf2, which is responsible for regulation of various antioxidant enzyme systems and protection of mitochondria from ROS-induced damage.
Keywords: metformin, rotenone, mitochondria, oxidative stress, Parkinson's disease
