**Acknowledgements**

binding sites leading to substitutions of these ions in many biological processes; this is due to

Arsenic (As) is a chemical element from group 15, and period 4 (p-block); it is contained in many minerals, but it also appear as a pure elemental crystal. As inhibits lipoic acid, which is a cofactor for pyruvate dehydrogenase into the citric acid cycle. Another important aspect is

tion of H2O2 is also increased, which lead to ROS production and oxidative stress. The frequency of human cancers is increased in the case of long term exposure at As probably due

Zhang Z and *colab*. showed that As can activate p47(phox) and p67(phox), proteins which activate NADPH oxidase and it generate ROS in DLD1 cells. It was found that tumor volumes of group treated with As were much larger than those without As treatment. Many researchers found that ROS have a role in the initiation of cellular injury induced by As, which can lead to cancer development. ROS induce direct cellular injury, which may start a set of radical reactions leading to an increase of secondary ROS generation. More than that, the increased ROS production may stimulate the inflammatory processes involving secretion of chemotactic factors, growth factors, proteolytic enzymes, lipoxygenases, and cyclooxygenase, inactivation of anti-proteolytic enzymes, and the release of signaling proteins. NADPH oxidase complex is an important physiological system for ROS production; As is highly capable of activating NADPH oxidase and disrupting of mitochondrias' membrane, leading to the generation of different ROS. It has been generally accepted that ROS are critical regulators for a wide range of cellular responses, from kinase activation, gene expression, DNA damage, cell proliferation,

Reactive oxygen species (ROS) represented a matter of debate/concern in the last years due to the dual role played by these compounds: beneficial effects at low concentrations (signal molecules, mediators of cellular homeostasis, activators of different enzymes) and deleterious effects at high concentrations (DNA and protein damage, lipid peroxidation and oxidative

The oxidative stress was described as an underlying mechanism in different pathologies, including: neurodegenerative diseases, multiple sclerosis, diabetes, atherosclerosis, ageing, chronic inflammatory diseases and cancer. In cancer development, a possible theory regards the activity of ROS as regulators of major signaling pathways: extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinases (PI3Ks) and transcription factors such as hypoxia-inducible factors (HIFs). In addition, it was demonstrated that the toxicity associated to heavy metals (lead, mercury, arsen, cadmium, thallium, bismuth, manganese, iron) is mediated via ROS: ROS generation, mitochondrial

3- decouples the oxidative phosphorylation leading to the inhibition of

, mitochondrial respiration, and ATP synthesis. The produc‐

the similarities of their electron structure [57].

to cell migration in the arsenic treated cells [59].

injury or inhibition of the antioxidant cellular systems.

the fact that AsO4

**7. Conclusions**

stress).

energy-linked reduction of NAD+

16 Toxicology Studies - Cells, Drugs and Environment

to the ROS production [58].

Financial support offered by the intern grant PII-C2-TC-2014-16498-10 "Victor Babes" Uni‐ versity of Medicine and Pharmacy, Timisoara, Romania.
