Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549

Abstract

We study the ameliorative potential of dimetylthiourea (DMTU), an OH• radical trapper and N-acetylcysteine (NAC), a glutathione precursor/H2O2 scavenger against titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes (MWCNTs) induced cyto-genotoxicity in cultured human lung cancer cells-A549. Cytogenotoxicity was induced by exposing the cells to selected concentrations (10 and 50 µg/ml) of either of TiO2-NPs or MWCNTs for 24 h. Anti-cytogenotoxicity effects of DMTU and NAC were studied in two groups, i.e., treatment of 30 minutes prior to toxic insult (short term exposure), while the other group received DMTU and NAC treatment during nanoparticles exposure, i.e., 24 h (long term exposure). Investigations were carried out for cell viability, generation of reactive oxygen species (ROS), micronuclei (MN), and expression of markers of oxidative stress (HSP27, CYP2E1), genotoxicity (P53) and CYP2E1 dependent n- nitrosodimethylamine-demethylase (NDMA-d) activity. In general, the treatment of both DMTU and NAC was found to be effective significantly against TiO2-NPs and MWCNTs induced cytogenotoxicity in A549 cells. Long-term treatment of DMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantly to both DMTU and NAC, but responses were chemical specific. In part, TiO2-NPs induced toxic responses were mediated through OH• radicals generation and reduction in the antioxidant defense system. While in the case of MWCNTs, adverse effects were primarily due to altering/hampering the enzymatic antioxidant system. Data indicate the applicability of human lung cancer cells-A549 as a pre-screening tool to identify the target specific prophylactic and therapeutic potential of drugs candidate molecules against nanoparticles induced cellular damages.

Peroxyacetyl nitrate-induced oxidative and calcium signaling events leading to cell death in ozone-sensitive tobacco cell-line

“…21,22 While some researchers questioned the specificity of DMTU, even today, many of medical, pharmacological and toxicological specialists rely on the effect of DMTU as "OH radical scavenger" to conclude the involvement of OH radicals in the DMTU-treated cells of human 23,24 and other mammals, 25 and microbes including green algae. 26 On the other hand, Wu et al 27 have recently employed DMTU as H 2 O 2 scavenger, for studying the involvement of H 2 O 2 in programmed cell death in wheat aleurone layers.…”

Amorphous silica nanoparticles trigger vascular endothelial cell injury through apoptosis and autophagy via reactive oxygen species-mediated MAPK/Bcl-2 and PI3K/Akt/mTOR signaling

“…[9][10][11] It has been reported to reduce cell damage induced by NPs including nano-titanium dioxide 12 and multi-walled carbon nanotubes. 13 However, the mechanisms underlying its beneficial effects are poorly defined. This study is an extension of our previous study, which aimed at fully understanding the effects and interaction mechanisms of SiNPs-induced disturbance of endothelial cell homeostasis, and also determining the therapeutic effects and possible mechanisms of NAC on attenuating the SiNPs-triggered ROS signaling in vascular endothelial cells.…”

Protective Effects of Erythropoietin and N-Acetylcysteine on Methotrexate-Induced Lung Injury in Rats

“…N-acetylcysteine (NAC) has been widely used as an antioxidant in vivo and in vitro (16)(17)(18). NAC plays an important role at protection of cell from oxidative stress by inhibiting the H^O^ formation in vitro.…”

“…NAC plays an important role at protection of cell from oxidative stress by inhibiting the H^O^ formation in vitro. NAC also increases the cellular GSH level by directing cystine into the GSH synthesis pathway (18).…”