Respiratory Safety Evaluation in Mice and Inhibition of Adenoviral Amplification in Human Bronchial Endothelial Cells Using a Novel Type of Chlorine Dioxide Gas Reactor.

Since the onset of the COVID-19 pandemic, there has been a growing demand for effective and safe disinfectants. A novel use of chlorine dioxide (ClO2) gas, which can satisfy such demand, has been reported. However, its efficacy and safety remain unclear. For the safe use of this gas, the stable release of specific concentrations is a must. A new type of ClO2 generator called Dr.CLOTM has recently been introduced. This study aimed to investigate: (1) the effects of Dr.CLOTM on inhibiting adenoviral amplification on human bronchial epithelial (HBE) cells; and (2) the acute inhalation safety of using Dr.CLOTM in animal models. After infecting HBE cells with a recombinant adenovirus, the inhibitory power of Dr.CLOTM on the virus was expressed as IFU/mL in comparison with the control group. The safety of ClO2 gas was indirectly predicted using mice by measuring single-dose inhalation toxicity in specially designed chambers. Dr.CLOTM was found to evaporate in a very constant concentration range at 0-0.011 ppm/m3 for 42 days. In addition, 36-100% of adenoviral amplification was suppressed by Dr.CLOTM, depending on the conditions. The LC50 of ClO2 gas to mice was approximately 68 ppm for males and 141 ppm for females. Histopathological evaluation showed that the lungs of female mice were more resistant to the toxicity from higher ClO2 gas concentrations than those of male mice. Taken together, these results indicate that Dr.CLOTM can be used to provide a safe indoor environment due to its technology that maintains the stable concentration and release of ClO2 gas, which could suppress viral amplification and may prevent viral infections.

NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases.

Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Mitochondrial dysfunction is linked to oxidative stress and reactive oxygen species (ROS) in neurotoxicity during AD. Impaired mitochondrial metabolism has been associated with mitochondrial dysfunction in brain damage of AD. While the role of NADPH oxidase 4 (NOX4), a major source of ROS, has been identified in brain damage, the mechanism by which NOX4 regulates ferroptosis of astrocytes in AD remains unclear. Here, we show that the protein levels of NOX4 were significantly elevated in impaired astrocytes of cerebral cortex from patients with AD and APP/PS1 double-transgenic mouse model of AD. The levels of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), a marker of oxidative stress-induced lipid peroxidation, were significantly also elevated in impaired astrocytes of patients with AD and mouse AD. We demonstrate that the over-expression of NOX4 significantly increases the impairment of mitochondrial metabolism by inhibition of mitochondrial respiration and ATP production via the reduction of five protein complexes in the mitochondrial ETC in human astrocytes. Moreover, the elevation of NOX4 induces oxidative stress by mitochondrial ROS (mtROS) production, mitochondrial fragmentation, and inhibition of cellular antioxidant process in human astrocytes. Furthermore, the elevation of NOX4 increased ferroptosis-dependent cytotoxicity by the activation of oxidative stress-induced lipid peroxidation in human astrocytes. These results suggest that NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in AD.