We wish to thank Dr. Frans Coenen (University of Liverpool) for kindly allowing us to use his software for our research. We also thank Takashi Matsuda and Kotaro Tamura

(Astellas Pharma Inc.) for their useful advices. “
“Heavy metals can be classified as potentially toxic (arsenic, cadmium, lead, etc.), probably essential (vanadium, cobalt) and essential (copper, zinc, iron, manganese, etc.). Toxic elements can be very harmful even at low concentration when ingested over find protocol a long time period [1]. They might come from the soil, environment, fertilizers and/or metal-containing pesticides, introduced during the production process or by contamination from the metal processing equipment. Food consumption had been identified as the major pathway of human exposure to toxic metals, compared with other ways of exposure such as inhalation and dermal contact [2]. Humans are constantly exposed to hazardous pollutants in the environment-for example, in the air, water, soil, rocks, diet or workplace. Trace metals are important in environmental Buparlisib clinical trial pathology because of the wide range of toxic reactions and their potential adverse effects on the physiological function of organ systems. Exposures to toxic trace metals have been the subject of numerous environmental and geochemical investigations, and many studies have been published

on the acute and/or chronic effects of high-level exposures to these types of agents; however, much fewer data are available concerning the health effects of low-dose chronic exposure to many trace metals [3]. Iron is an important trace element of the body, being found in functional form in hemoglobin, myoglobin, cytochrome enzymes with iron sulphur complexes [4]. Liver is one of the largest

organs in the human body and the main site for intense metabolism and excretion [5]. Hepatotoxicity is the most common finding in patients with iron overloading as liver is mainly the active storage site of iron in our body [6]. Hydroxy radical may form due to excess iron concentration in kidney that leads to progression of tubular injury. Clinical evidence showed that iron deposition in kidney associated with the anemia during kidney diseases selleck screening library [7]. Although an optimum level of iron is always maintained by the cells to balance between essentiality and toxicity, in some situations it is disrupted, resulting in iron overload which is associated to the oxidative stress induced disorders including anemia, heart failure, hepatocellular necrosis and cirrhosis [8]. In iron overload-induced diseases, iron removal by iron chelation therapy is an effective life-saving strategy. Iron overload increases the formation of reactive oxygen species (ROS) which involves the initiation of lipid peroxidation, protein oxidation and liver fibrosis.