Role of melatonin and quercetin as countermeasures to the mitochondrial dysfunction induced by titanium dioxide nanoparticles

Due to the growing commercialization of titanium dioxide nanoparticles (TNPs), it is necessary to use these particles in a manner that is safe, healthy and environmental friendly. Through reactive oxygen species (ROS) generation, it has been discovered that TNPs have a harmful effect on the brain. The aim of this study is to provide valuable insights into the possible mechanisms of TNPs induced mitochondrial dysfunction in brain and its amelioration by nutraceuticals, quercetin (QR) and melatonin (Mel) in in vitro and in vivo conditions. Whole brain mitochondrial sample was used for in-vitro evaluation. Pre-treatment of QR (30 μM) and Mel (100 μM) at 25 °C for 1 h was given prior to TNPs (50 μg/ml) exposure. For in-vivo study, male Wistar rats were divided into four groups. Group I was control and group II was exposed to TNPs (5 mg/kg b.wt., i.v.). QR (5 mg/kg b.wt.) and Mel (5 mg/kg b.wt.) were given orally as pre-treatment in groups III and IV, respectively. Biochemical parameters, neurobehavioural paradigms, mitochondrial respiration, neuronal architecture assessment were assessed. QR and Mel restored the mitochondrial oxidative stress biomarkers in both the studies. Additionally, these nutraceuticals resuscitated the neurobehavioural alterations and restored the neuronal architecture alterations in TNPs exposed rats. The mitochondrial dysfunction induced by TNPs was also ameliorated by QR and Mel by protecting the mitochondrial complex activity and mitochondrial respiration rate. Results of the study demonstrated that QR and Mel ameliorated mitochondrial mediated neurotoxic effects induced by TNPs exposure.