Biochemical and medical importance of vanadium compounds.

Abstract

Vanadium belongs to the group of transition metals and is present in the air and soil contaminants in large urban agglomerations due to combustion of fossil fuels. It forms numerous inorganic compounds (vanadyl sulfate, sodium metavanadate, sodium orthovanadate, vanadium pentoxide) as well as complexes with organic compounds (BMOV, BEOV, METVAN). Depending on the research model, vanadium compounds exhibit antitumor or carcinogenic properties. Vanadium compounds generate ROS as a result of Fenton's reaction or of the reaction with atmospheric oxygen. They inactivate the Cdc25B(2) phosphatase and lead to degradation of Cdc25C, which induces G(2)/M phase arrest. In cells, vanadium compounds activate numerous signaling pathways and transcription factors, including PI3K-PKB/Akt-mTOR, NF-κB, MEK1/2-ERK, that cause cell survival or increased expression and release of VEGF. Vanadium compounds inhibit p53-dependent apoptosis and promote entry into the S phase of cells containing functional p53 protein. In addition, vanadium compounds, in particular organic derivatives, have insulin-mimetic and antidiabetic properties. Vanadium compounds lower blood glucose levels in animals and in clinical trials. They also inhibit the activity of protein tyrosine phosphatase 1B. By activating the PI3K-PKB/Akt pathway, vanadium compaunds increase the cellular uptake of glucose by the GLUT4 transporter. The PKB/Akt pathway is also used to inactivate glycogen synthase kinase-3. The impact of vanadium compounds on inflammatory reactions has not been fully studied. Vanadium pentoxide causes expression of COX-2 and the release of proinflammatory cytokines in a human lung fibroblast model. Other vanadium compounds activate NF-κB in macrophages by activating IKKβ.

Vanadium and proteins: Uptake, transport, structure, activity and function

“…Prediction of the in vivo effect of these compounds is not straightforward as their interactions with enzymes disseminates to so many distinct systems and at so many levels of the cell cycle [31].…”

“…However, the complexity of their effects and the lack of knowledge in some areas such as their effects on e.g. the immune systems and inflammatory processes, or in their use in long-term administration therapies, and of the risks associated with their potential carcinogenic effect and disorders in the free-radical background in cells, require a much deeper understanding and evaluation of the balance between beneficial and toxic effects of their use [31].…”

Vanadium(IV)-chlorodipicolinate inhibits 3T3-L1 preadipocyte adipogenesis by activating LKB1/AMPK signaling pathway

“…Evidences from in vivo and in vitro studies have demonstrated that vanadium compounds exert various insulin-mimetic properties [24][25][26][27][28] and anti-diabetic effects [29][30][31][32][33]. These include their ability to improve glucose homeostasis and insulin resistance in animal models of type 1 and type 2 diabetes mellitus [34][35][36][37][38][39][40][41].…”

Thirty years through vanadium chemistry

“…Progress in the chemistry of vanadium related to the search of therapeutic applications has been exponential during the last 10-15 years, and several reviews have been published, a few of them during the last five years [1,62,[173][174][175][176][177][178][179][180][181][182][183].…”

“…While this potentiates their application in therapeutics, namely the treatment of diabetes, it may also exert nonspecific opposite effects on several cell functions. Moreover, still not much is known regarding global toxicity issues and effects of vanadium on the immune system and inflammatory reactions, particularly if long-term administration is required [181]. Namely vanadium-induced oxidative stress [196][197][198] is probably a major factor, namely at the level of the mitochondria.…”