Is there a Role for Sodium Orthovanadate in the Treatment of Diabetes?

Rana, Divya; Kumar, Anoop

doi:10.2174/1573399814666180903162556

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…V is an element having multiple possible roles in animals and human. Although toxic effects induced by high doses have been reported, many studies suggested the opportunity of exploiting V-based products as metalpharmaceuticals [ 9 ]. It is well known that metals released in the environment, in a close contact with organisms, can accumulate along the food chain.…”

Section: Discussionmentioning

confidence: 99%

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Toxicity of Vanadium during Development of Sea Urchin Embryos: Bioaccumulation, Calcium Depletion, ERK Modulation and Cell-Selective Apoptosis

Chiarelli

Scudiero²,

Memoli³

et al. 2022

IJMS

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Vanadium toxicology is a topic of considerable importance as this metal is widely used in industrial and biomedical fields. However, it represents a potential emerging environmental pollutant because wastewater treatment plants do not adequately remove metal compounds that are subsequently released into the environment. Vanadium applications are limited due to its toxicity, so it is urgent to define this aspect. This metal is associated with sea urchin embryo toxicity as it perturbs embryogenesis and skeletogenesis, triggering several stress responses. Here we investigated its bioaccumulation and the correlation with cellular and molecular developmental pathways. We used cytotoxic concentrations of 1 mM and 500 μM to perform quantitative analyses, showing that vanadium accumulation interferes with calcium uptake during sea urchin development and provokes a disruption in the biomineralization process. At the end of the whole treatment, the accumulation of vanadium was about 14 and 8 μg for embryos treated respectively with 1 mM and 500 μM, showing a dose-dependent response. Then, we monitored the cell signaling perturbation, analyzing key molecular markers of cell survival/cell death mechanisms and the DNA fragmentation associated with apoptosis. This paper clarifies vanadium’s trend to accumulate directly into embryonic cells, interfering with calcium uptake. In addition, our results indicate that vanadium can modulate the ERK pathway and activate a cell-selective apoptosis. These results endorse the sea urchin embryo as an adequate experimental model to study metal-related cellular/molecular responses.

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Section: Discussionmentioning

confidence: 99%

“…V compounds represent an encouraging search field in medicine as several studies have revealed the potential role of V-based products for the treatment of several pathologies (dysmetabolic syndromes, neurodegenerative diseases and heart disorders) [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Toxicity of Vanadium during Development of Sea Urchin Embryos: Bioaccumulation, Calcium Depletion, ERK Modulation and Cell-Selective Apoptosis

Chiarelli

Scudiero²,

Memoli³

et al. 2022

IJMS

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“…Some preliminary studies of vanadium compounds as potential antidiabetic agents but no phase 2 trials (Rana & Kumar, 2018;Thompson & Orvig, 2006). Vanadium compounds are sold as dietary supplements.…”

Section: Sodium Orthovanadatementioning

confidence: 99%

Mini‐review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility

Curtis

Bandyopadhyay²

2020

Annals of Human Genetics

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A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.

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“…Recently, V derivatives have been considered as potential therapeutic factors for several diseases (e.g., obesity, diabetes, cancer, neurodegenerative, and heart disorders) [12][13][14]. For all these reasons, many studies on V compounds were conducted to investigate their therapeutic and/or toxicological effects [15].…”

Section: Introductionmentioning

confidence: 99%

“…For all these reasons, many studies on V compounds were conducted to investigate their therapeutic and/or toxicological effects [15]. There is a considerable interest on Na 3 VO 4 due to its role in the treatment of diabetes [12], even if its toxic effects in terms of stress, autophagy, and apoptosis induction were recently reported [16]. The V 2 O 5 is instead used as a catalyst for the conversion of sulphur dioxide to trioxide when producing sulphuric acid and maleic anhydride, which is a chemical required to produce polyester resins and fiberglass [17].…”

Section: Introductionmentioning

confidence: 99%

Vanadium Toxicity Monitored by Fertilization Outcomes and Metal Related Proteolytic Activities in Paracentrotus lividus Embryos

Chiarelli

Martino

Roccheri

et al. 2022

Toxics

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Metal pharmaceutical residues often represent emerging toxic pollutants of the aquatic environment, as wastewater treatment plants do not sufficiently remove these compounds. Recently, vanadium (V) derivatives have been considered as potential therapeutic factors in several diseases, however, only limited information is available about their impact on aquatic environments. This study used sea urchin embryos (Paracentrotus lividus) to test V toxicity, as it is known they are sensitive to V doses from environmentally relevant to very cytotoxic levels (50 nM; 100 nM; 500 nM; 1 µM; 50 µM; 100 µM; 500 µM; and 1 mM). We used two approaches: The fertilization test (FT) and a protease detection assay after 36 h of exposure. V affected the fertilization percentage and increased morphological abnormalities of both egg and fertilization envelope, in a dose-dependent manner. Moreover, a total of nine gelatinases (with apparent molecular masses ranging from 309 to 22 kDa) were detected, and their proteolytic activity depended on the V concentration. Biochemical characterization shows that some of them could be aspartate proteases, whereas substrate specificity and the Ca2+/Zn2+ requirement suggest that others are similar to mammalian matrix metalloproteinases (MMPs).

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Is there a Role for Sodium Orthovanadate in the Treatment of Diabetes?

Abstract: The sodium orthovanadate could be developed as an anti-diabetic agent. However, further studies are required to confirm its safety profile in the treatment of diabetes mellitus before starting a clinical trial.

Cited by 12 publications

References 30 publications

Toxicity of Vanadium during Development of Sea Urchin Embryos: Bioaccumulation, Calcium Depletion, ERK Modulation and Cell-Selective Apoptosis

Toxicity of Vanadium during Development of Sea Urchin Embryos: Bioaccumulation, Calcium Depletion, ERK Modulation and Cell-Selective Apoptosis

Mini‐review: Role of the PI3K/Akt pathway and tyrosine phosphatases in Alzheimer's disease susceptibility

Vanadium Toxicity Monitored by Fertilization Outcomes and Metal Related Proteolytic Activities in Paracentrotus lividus Embryos

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