Mitochondrial dysfunction in titanium dioxide nanoparticle-induced neurotoxicity.

Nanotechnology has emerged as a field of scientific innovation which has opened up a plethora of concerns for the potential impact on human and environment. Various toxicological studies have confirmed that nanoparticles (NPs) can be potentially hazardous because of their unique small size and physico-chemical properties. With the wide applications of titanium dioxide nanoparticles (TNPs) in day-to-day life in form of cosmetics, paints, sterilization and so on, there is growing concern regarding the deleterious effects of TNPs on central nervous system. Mitochondria is an important origin for generation of energy as well as free radicals and these free radicals can lead to mitochondrial damage and finally lead to apoptosis. The objective of our study was to elucidate the potential neurotoxic effect of TNPs in anatase form. Oxidative stress was determined by measuring lipid peroxidation and protein carbonyl content which was found to be significantly increased. Reduced glutathione content and major glutathione metabolizing enzymes were also modulated signifying the role of glutathione redox cycle in the pathophysiology of TNPs. Mitochondrial complexes were also modulated from the exposure to TNPs. The present study indicates that nanosize TNPs may pose a health risk to mitochondrial brain with the generation of reactive oxygen species, and thus NPs should be carefully used.

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

AIM: 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. MATERIALS AND METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Results of the study demonstrated that QR and Mel ameliorated mitochondrial mediated neurotoxic effects induced by TNPs exposure.

Progression of Chronic Pancreatitis to Pancreatic Cancer: Is There a Role of Gene Mutations as a Screening Tool?

OBJECTIVES: Early detection of pancreatic ductal adenocarcinoma still remains a challenge. Patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer. Mutations in oncogenes and/or tumor suppressor genes play a role in development of pancreatic ductal adenocarcinoma. This study assessed mutations in KRAS and p53 gene in blood as a screening tool for malignant transformation in CP patients. METHODS: This was a cohort, single-center study including 294 CP patients. DNA was isolated from plasma of CP patients, and KRAS mutations were identified using polymerase chain reaction-restriction fragment length polymorphism. Patients with positive KRAS mutation were screened for malignancy using positron emission tomography or endoscopic ultrasound. Mutations in p53 gene were analyzed by sequencing. Tissue samples from CP and pancreatic cancer patients were also tested for mutations in KRAS and p53 genes. RESULTS: The plasma samples of 64 CP patients were positive for KRAS mutation, and 4 had mutation in p53 gene also. No patient positive for KRAS mutation and/or p53 mutation was found to have malignant transformation. CONCLUSION: Detection of KRAS or p53 mutation in plasma is not an effective screening tool for pancreatic cancer because accumulation of multiple mutations is required for malignant transformation in the pancreas.