Oxidative Stress and Vanadium

Air pollution is a worldwide health problem, and metals are one of the various air pollutants to which living creatures are exposed. The pollution by metals such as: lead, cadmium, manganese, and vanadium have a common mechanism of action: the production of oxidative stress in the cell. Oxidative stress favors the production of free radicals, which damage biomolecules such as: DNA, proteins, lipids, and carbohydrates; these free radicals produce changes that are observed in different organs and systems. Vanadium is a transition element delivered into the atmosphere by the combustion of fossil fuels as oxides and adhered to the PM enters into the respiratory system, then crosses the alveolar wall and enters into the systemic circulation. In this chapter, we will review the oxidative stress induced by vanadium—as a common mechanism of metal pollutants—; in addition, we will review the protective effect of the antioxidants (carnosine and ascorbate)

Pharmacological and toxicological effects of copper and vanadium using in vitro and in vivo models of Parkinson’s Disease

Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects: notably, oxidative damage and mitochondria dysfunction, leading to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Exposure to heavy metals and some environmental toxicants have been associated for many years with this disease pathogenesis. Raised iron levels have been consistently observed in the nigrostriatal pathway in PD cases. This thesis focused on the effects of an endogenous heavy metal micronutrient (copper - Cu) and an exogenous environmental heavy metal (vanadium - Vd), and explored the interplay with iron (Fe), focusing for the first time on sub-toxic effects of these metals upon neuronal cell oxidative and ER stress, differentiation, calcium signalling, motor activity, oxidative stress and lifespan in an in vitro (Catecholaminergic a-differentiated (CAD) cells) and in vivo (Drosophila melanogaster) model of PD respectively. Undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells and this susceptibility was modulated by iron. Both a natural (Aloysia citrodora) and synthetic iron chelator, Deferoxamine (DFO), significantly and efficiently protected against chronic sub-toxic Vd-induced mitochondrial oxidative stress in contrast, iron chelation exacerbated the oxidative stress elicited by Cu. Low dose Cu had no significant effect upon metabolic rate (in both differentiated and differentiating CAD cells) but significantly protected undifferentiated cells, decreased potassium chloride (KCl)-induced depolarisation and positively enhanced the expression of MAP2 in differentiated cells In vivo exposure of Drosophila melanogaster (DM) to sub-toxic doses of Vd had a range of differential biochemical and behavioural effects upon wild-type (WT) and PD Pink-1B9 drosophila fly models. In pink-1 flies, exposure to chronic low dose of vanadium exacerbated the existing motor deficits, reduced survival, increased the production of reactive oxygen species (ROS), as well as T-SH and a reduction in survival. In WT, it caused an enhancement in motor activity (like L-dopa), in parallel with a reduction in brain RONS generation and increased total thiol levels (T-SH), with a resulting lifespan extension. Both Aloysia citrodora L, and DFO significantly protected against the PD-like phenotypes in both models. The results accrued in this thesis favours the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD

Cotherapy of Tiron and selenium against vanadium induced toxic effects in lactating rats

Background: Vanadium is an important environmental and industrial pollutant. It has a status of reproductive toxicant and is reported to cross placental barrier. Objective: The current study was performed to assess the therapeutic efficacy of Tiron and its combination with selenium against vanadium induced toxicity in lactating and suckling rats. Materials and Methods: Rats were exposed to vanadium at a dose of 7.5 mg/kg/day (p.o.) for 20 days from 0 day of post partom (p.p.). Tiron (606 mg/kg/day, i.p.) and selenium (0.5 mg/kg/day, p.o.) were administered for 5 days on 21-25 day PP. Results: Vanadium exposure decreased blood sugar level while serum transaminases and serum alkaline phosphatase showed increased values significantly (p≤0.01). Elevation in glycogen content of liver and kidney of suckling and kidney of lactating rats was found after toxicant administration. Toxicant intoxication increased the enzymatic activity of acid phosphatase in liver of suckling and lactating and kidney of suckling rats. On the contrary alkaline phosphatase and adenosine triphosphatase activities were inhibited significantly (p≤0.01) in all the organs. Lipid peroxidation was enhanced whereas glutathione was reduced significantly in liver of suckling and lactating rats (p≤0.01). Vanadium also caused histopathological lesions. Therapies of Tiron per se and Tiron along with selenium maintained almost all blood and tissue biochemical parameters towards normal. Tiron along with selenium reduced vanadium induced lesions in lactating and sucklings rats. Conclusion: Tiron along with selenium is more effective than Tiron alone against vanadium induced toxic effect on lactating and suckling rats

Cotherapy of Tiron and selenium against vanadium induced toxic effects in lactating rats

Background: Vanadium is an important environmental and industrial pollutant. It has a status of reproductive toxicant and is reported to cross placental barrier. Objective: The current study was performed to assess the therapeutic efficacy of Tiron and its combination with selenium against vanadium induced toxicity in lactating and suckling rats. Materials and Methods: Rats were exposed to vanadium at a dose of 7.5 mg/kg/day (p.o.) for 20 days from 0 day of post partom (p.p.). Tiron (606 mg/kg/day, i.p.) and selenium (0.5 mg/kg/day, p.o.) were administered for 5 days on 21-25 day PP. Results: Vanadium exposure decreased blood sugar level while serum transaminases and serum alkaline phosphatase showed increased values significantly (p≤0.01). Elevation in glycogen content of liver and kidney of suckling and kidney of lactating rats was found after toxicant administration. Toxicant intoxication increased the enzymatic activity of acid phosphatase in liver of suckling and lactating and kidney of suckling rats. On the contrary alkaline phosphatase and adenosine triphosphatase activities were inhibited significantly (p≤0.01) in all the organs. Lipid peroxidation was enhanced whereas glutathione was reduced significantly in liver of suckling and lactating rats (p≤0.01). Vanadium also caused histopathological lesions. Therapies of Tiron per se and Tiron along with selenium maintained almost all blood and tissue biochemical parameters towards normal. Tiron along with selenium reduced vanadium induced lesions in lactating and sucklings rats. Conclusion: Tiron along with selenium is more effective than Tiron alone against vanadium induced toxic effect on lactating and suckling rats