BROCHURE

Organo Vanadium 4

ORGANO-VANADIUM

Classtitle

FallQuarter 2016

Chemicalstructure, description and physical-chemical properties.

Chemicalstructure of organovanadium compounds constitutes a chemical bondbetween carbon and vanadium.

Themost common OVCs include bis(maltoalto)oxy vanadium (IV), Vanadylacetylacetonate and the vanadyl 3-

Ethylacetylacetonate.

Themost studied OVC, concerning its anti-diabetic properties is thebis(maltoalto)oxy vanadium (IV), commonly abbreviated as VM.

Thefollowing structures portray examples of vanadium salts with organicmoieties.

bis(maltolato)oxyvanadium(IV) (BMOV)

Vanadylacetylacetonate (VAC)

Vanadylethyl acetylacetonate

Physico-chemicalproperties

  • Undergoes thermal decomposition

  • Some are catalytic (Clark, et al., 2013)

  • Some act as chelating agents

  • Some may undergo sublimation

  • Have insulin-like properties

  • Have mimetic properties

Sources/Emissions

OVCsare found in natural and anthropogenic sources.

Theyare released into the water, atmosphere, and land from the sourcesmentioned earlier.

Exposures/biomarkers(in the US)

Drugsare a critical source of organo-vanadium compounds. For example,bis(maltolato)oxy vanadium (IV) or vanadyl acetylacetonate are usedto combat diabetes and cancer. Therefore, patients utilizing thesedrug compounds are exposed to the vanadium.

Exposureto vanadium compounds is via inhalation, dermal or through oralingestion, and as a result, biomarkers of effect may be identified. Instances of tissue dysfunction, hypertension or reductions in lungcapacity, may be present (USDepartment of Health and Human Services Public Health Service Agencyfor Toxic Substances and Disease Registry, 2012).An increment in vanadium levels noted in the blood, serum, andurine are critical pointers of exposure to vanadium.

Greentongue cases, alteration in the finger nail cysteine levels, and highvanadium concentrations in the hair are also key biomarkers ofeffect.

Healtheffects information (Acute and chronic, risk assessment

AsDrugs:

Organovanadiumcompounds are noted to have effects that are insulin-like in systemsthat are both in vitro and in vivo. The OVCs also play a role in theimprovement of glucose homeostasis. The OVCs play a part in theimprovement of insulin resistance in diabetes mellitus models. Theyalso promote insulin sensitivity in both the muscle and the liver.The OVCs are also noted to promote cell differentiation andproliferation (Ferodova et al., 2013).

Whenbis(maltolato)oxy vanadium (IV) is administered in a rather acutemanner, it is noted to boost its effectiveness. The effectiveness isin the sense of the reduction in glucose levels. This is especiallyso when it comes to the reduction of glucose levels. Theeffectiveness is comparable to the vanadium salts (VS), especially,the inorganic analog of the VM.

Whenaddressing the long-term perspective, of the exposure of VM, noeffects have been noted.

PBPKmodels are employed in the determination of toxic moieties of achemical that are delivered through various combinations ofadministration routes.

Toxicmechanism of action andmetabolism

Themechanism of toxicity of the OVCs is unknown given that thesecompounds are considered to be safer as opposed to vanadium saltsthat are inorganic. The OVCs do not cause any gastrointestinalirritation and toxicity of hepatic or renal perspectives, whichexceeds the quantities that are usually found in the environment.

Susceptiblegroups

Thevulnerable groups arethe individuals who have type II diabetes, who are under the OVCstherapy.

Healtheffects information (Acute and chronic, risk assessment

Aspollutants:

TheOVCs cause respiratory effects.

Gastrointestinaleffects are also notable upon the ingestion of vanadium compounds

Toxicmechanism of action andmetabolism

Airwayirritation is noted in individuals subjected to acute levels ofvanadium

Intermediateexposure of vanadium compounds is limited to studies conducted inrats

Toxicityin humans has been noted after intermediate oral exposure

Chronicduration of exposure has been noted to have respiratory effects onlab animals

Nostudies associated with oral toxicity after ingestion of vanadiumcompounds has been noted.

Carcinogenicityhas not been assessed in humans

Themechanism of functioning takes note of the oxidation state ofvanadium, the tetravalent and the pentavalent form i.e. vanadyl andthe vanadate ions respectively.

Thevanadium, in either of the states as mentioned above, readily bindswith the transferrin protein and as a result, transferred to theerythrocytes. These oxidation states allow vanadium to exist ineither the bound or unbound form, while in the plasma.

Vanadylions, compared to the vanadate ones, undergo slow uptake into theerythrocytes. The reason for the slow uptake of the vanadyl ions hasbeen presumed to be as a result of the time that is required for itsoxidation to the vanadate ions. Because of the above occurrence, inthe initial stages, vanadyl ions undergo fast blood clearance whichstabilizes with the development of an oxidation balance.

Thetoxicity mechanism of vanadium indicates that it interferes with thephosphatases, ATPases and the enzymes that are associated withphosphate transfer.

Vanadiumcompounds, as earlier mentioned, are related to insulin propertiesthat are mimetic (Mozaffari, 2013).

Thesecompounds are also noted to stimulate enzymes like NADPH oxidase andadenylate cyclase, and tyrosine kinase phosphorylase.

Susceptiblegroups

Individualsthat are exposed to vanadium pentoxide, a product found after thecombustion of organic anthropogenic vanadium, are vulnerable topossible toxicity (USDepartment of Health and Human Services Public Health Service Agencyfor Toxic Substances and Disease Registry, 2012).

Childrenare susceptible from exposures to the germ cell of their parent.However, certain characteristics in their development may increase orreduce susceptibility.

Laboratoryanimals utilized in the studies are susceptible.

Thepeer reviewed article that was studied was on the health effects oforganovanadium compounds by Mehdi,and Srivastava, (2005).The journal commenced by acknowledging the fact that vanadiumcompounds, in trace amount were noted to have insulin-like effectseither in systems that are in vitro or in vivo. These compounds arealso noted to play a critical role in enhancing glucose homeostasis.The information indicated by the authors was that organovanadiumcompounds as compared to inorganic vanadium salts were noted to haveno toxicity effects, when administered as drugs to combat diabetes.

Themethods that were incorporated in the study identified in thepeer-reviewed journal were to ascertain whether the insulin mimeticand the antidiabetic roles of the OVC had a link with their abilitiesto promote GSK-3 phosphorylation and PKB. The methods utilized werecell culture, immune-blotting, PTPase action and immunoprecipitation.

Theresults that were identified indicated that the OVCs, BMOV, and VACwere more powerful in the enhancement of PKP phosphorylation ascompared to the VS. VAC, compared to BMOV and the VS was powerful inpromoting GSK phosphorylation.

BothVAC and BMOV were noted to promote tyrosyl phosphorylation of IR,while VS were ineffective in this function.

Theauthors concluded that OVCs were more potent as drugs as compared tothe VS.

Theinhibitory function of the OVC on PTPases, and the increment ofprotein tyrosine phosphorylation were thought to play a role in thetriggering of duties which lead to the up-regulation of PKB which wascritical in the improvement of glucose homeostasis function.

References

  1. Fedorova, E. V., Buryakina, A. V., Vorobieva, N. M., &amp Baranova, N. I. (2013). The vanadium compounds: chemistry, synthesis, insulinomimetic properties. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 7(4), 259-270.

  2. Mehdi, M. Z., &amp Srivastava, A. K. (2005). Organo-vanadium compounds are potent activators of the protein kinase B signaling pathway and protein tyrosine phosphorylation: mechanism of insulinomimesis. Archives of biochemistry and biophysics, 440(2), 158-164.

  3. US Department of Health and Human Services Public Health Service Agency for Toxic Substances and Disease Registry.

(2012).TOXICOLOGICAL PROFILE FOR VANADIUM

  1. Clark, R. J. H., Brown, D., Bailar,

J.C., Emeléus, H. J., &amp Nyholm, R. (2013). The Chemistry ofVanadium, Niobium, and Tantalum: Pergamon Texts in InorganicChemistry.

  1. Mozaffari, M. S. (2013). New strategies to Advance Pre/Diabetes care: Integrative approach by PPPM. Dordrecht: Springer.