Logo-hpp
2023: Two-year Impact Factor: 2.4
Scopus Journal Metrics
CiteScore (2023):7.1
 
Platinum
Open Access

Health Promotion Perspectives. 12(2):122-130. doi: 10.34172/hpp.2022.16

Systematic Review

Vanadium and biomarkers of inflammation and oxidative stress in diabetes: A systematic review of animal studies

Faezeh Ghalichi 1ORCID logo, Alireza Ostadrahimi 2, Maryam Saghafi-Asl 3, *ORCID logo
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Clinical Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
3Nutrition Research Center, Drug Applied Research Center, Department of Clinical Nutrition, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding Author: Maryam Saghafi-Asl, Email: saghafiaslm@gmail.com

Abstract

Background: Oxidative stress has a significant role in the commencement and development of hyperglycemia. Vanadium, as a transitional metal with redox properties, enters the redox process, produces free radicals, and distracts the pro-antioxidant balance. The present animal systematic review aimed to assess the effect of vanadium supplementation on inflammation and oxidative stress biomarkers in diabetes-induced animals.

Methods: A systematic search was conducted using the PubMed, Scopus, and web of science databases from 1990 to 2021, according to the inclusion and exclusion criteria. The search strategy was based on the guidelines for systematic review of animal experiments and Preferred Reporting Items for Systematic Reviews (PRISMA). Criteria for eligibility were animal-based studies, evaluating the therapeutic effects of vanadium on inflammatory and oxidative stress biomarkers in diabetes. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool was used for assessing the methodological quality of included studies.

Results: In the present study, 341 articles were evaluated out of which 42 studies were eligible for inclusion. The majority of the studies confirmed the advantageous properties of vanadium on inflammatory and oxidative stress biomarkers. A minor risk of bias was reported, based on the SYRCLE’s tool.

Conclusion: According to the findings, well-designed clinical trials are warranted to assess the long-lasting effects of various vanadium compounds on inflammatory and oxidative stress biomarkers.

Keywords: Systematic review, Animals, Diabetes mellitus, Inflammation, Oxidative stress

Copyright

© 2022 The Author(s).
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction

Type 2 diabetes mellitus (T2DM), represents nearly 95% of all cases of DM and is characterized by insulin resistance or a decline in β-cells’ ability to secrete insulin.1 In chronic hyperglycemia, glucose auto-oxidation leads to abundant production of oxygen-free radicals in the mitochondria due to major oxygen usage, high redox reactions, mitochondrial-fission state, and failure of the antioxidant defense system.2-4 Nevertheless, oxidative stress has a significant role in the commencement and ongoing of hyperglycemia, as well. In general, the inequity of reactive oxygen species (ROS) production and elimination is described as oxidative stress.1 ROS production leads to the impairment of nuclear deoxyribonucleic acid (DNA). Additionally, it stimulates nuclear poly (ADP-ribose) polymerase (PARP), prevents glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, and shunts primary glycolytic substrates into pathogenic signaling pathways via the activation of I) the polyol, II) Protein kinase C (PKC), and III) glycation end-products (AGE) pathways.5

The signaling pathways mentioned above augment ROS formation and stimulate inflammation. The polyol pathway intensifies ROS production using nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), and aggregating consequent nicotinamide adenine dinucleotide (NADH) oxidation. In addition, hyperglycemia reinforces inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) expression. Inhibition of GAPDH leads to dihydroxyacetone phosphate construction, as well as PKC and AGE increase. Such events consequently induce NADPH oxidase and the expression of inflammatory factors and decline endothelial nitric oxide synthase stimulation. Also, PKC stimulates insulin resistance via preventing downstream expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway (PI3K-Akt).4,5

Cellular ROS concentration is detected by the production and clearance rate of ROS. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) are substrates that scavenge free radicals or inhibit their conversion to toxic derivatives.6 Thus, modulating these enzymes protect the cellular antioxidant system from oxidative stress.

Since 1970s, the insulin-mimetic or insulin-enhancing properties of vanadium have been discussed and it has been considered as a therapeutic agent against diabetes.7 Vanadium, as a transitional metal with redox properties, enters the redox process, produces free radicals, and distracts the pro-antioxidant balance in the cell. Vanadium is a scavenger of superoxide radicals, and declines antioxidant enzymes such as SOD, GPx, CAT, and GR in erythrocytes,8-11 liver,12-22 kidneys,14,19,20,22 heart,22 brain,22,23 pancreas16,20,24 and testes25 of rats. Based on the results of multiple studies, vanadium complexes increase the action of GPx and demolish the effect of ROS in diabetic-induced rats.6,8,22

Vanadium prevents protein tyrosine phosphatase activity and helps glucose transporter 4 translocation.26 Redox regulation inhibits PTP-1B activation. Due to the insulin-stimulating properties of NAD(P)H oxidase homolog Nox 4, it modulates H2O2 and plays an essential role in insulin signaling via modulating PTP-1B transcription.27 The complications of diabetes are directly associated with oxidative stress; hence, substrates reducing oxidative stress, are also beneficial for the complications of diabetes.28

The beneficial effects of vanadium in declining hyperglycemia have already been reported in experimental and clinical trials.29,30 However, the objective of the current animal-based systematic review was to put together experimental evidence to present a thorough assessment of the effects of vanadium administration on inflammatory and oxidative stress biomarkers in diabetes-induced animals.


Material and Methods

Search strategy

The Preferred Reporting Items for Systematic Reviews (PRISMA) was implicated in this systematic review.31 PubMed, Scopus, and Web of Science databases were used for searching animal-based studies evaluating the effect of vanadium administration on inflammatory and oxidative stress biomarkers among diabetic animals from 1990 to 2021 (Table 1).32-34 Language restriction was not considered during the search strategy.

Table 1. Search strategy according to database filters
Database Search items
PubMed(("Vanadium"[Mesh] OR "Vanadium Compounds"[Mesh]) OR (vanadium[Title/Abstract])) AND ((((((("Diabetes Mellitus, Type 2"[Mesh]) OR "Obesity"[Mesh]) OR "Glucose Intolerance"[Mesh]) OR ( "Diabetes Mellitus"[Mesh] OR "Diabetes, Gestational"[Mesh] OR "Diabetes Mellitus, Type 1"[Mesh] OR "Diabetes Mellitus, Experimental"[Mesh] )) OR "Insulin"[Mesh]) OR "Glycated Hemoglobin A"[Mesh]) OR ((((((((Diabetes[Title/Abstract]) OR (obesity[Title/Abstract])) OR ("glucose intolerance"[Title/Abstract])) OR (Insulin[Title/Abstract])) OR ("Glycated hemoglobin A"[Title/Abstract])) OR (HbA1c[Title/Abstract])) OR (prediabetes[Title/Abstract])) OR (overweight[Title/Abstract])))
Scopus((TITLE-ABS-KEY(Vanadium))) AND ((TITLE-ABS-KEY(Diabetes) OR TITLE-ABS-KEY (Obesity) OR TITLE-ABS-KEY (Overweight) OR TITLE-ABS-KEY (“Glucose Intolerance”) OR TITLE-ABS-KEY (Insulin) OR TITLE-ABS-KEY (“Glycated hemoglobin A”) OR TITLE-ABS-KEY (HBA1C) OR TITLE-ABS-KEY (Prediabetes)
Web of Science((Vanadium)) AND ((Diabetes) OR (Obesity) OR (Overweight) OR (“Glucose Intolerance”) OR (Insulin) OR (“Glycated hemoglobin A”) OR (HBA1C) OR Prediabetes))

Inclusion criteria

Eligible studies for including in this systematic review obeyed the PICOS criteria, as below35:

  • Participants: Diabetes-induced laboratory animals.

  • Interventions: Vanadium administration.

  • Comparisons: Diabetic control animals, consuming a regular diet.

  • Outcomes: Measuring inflammatory and oxidative stress biomarkers.

  • Study design: Animal studies assessing the effect of vanadium administration in diabetic-induced animals.

Exclusion criteria

Studies assessing the effects of vanadium compounds on glycemic markers and lipid profile were excluded in this systematic review. Also, studies with invasive surgical procedures or certain diets were excluded.

Study selection

Animal studies were screened individually by two investigators, according to the inclusion and exclusion criteria. At first, the titles and abstracts of selected studies were assessed; afterwards, the full texts were read carefully. In the end, the papers were monitored for final detection. Disagreements regarding selecting certain studies for inclusion were determined by discussion among investigators.

Data extraction

A pre-standardized data extraction form was independently administered by two authors for extracting data. In the end, a third author was responsible for rechecking extracted data.

Assessment of methodological quality

The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)’s Risk of Bias (RoB) tool36 was used for evaluating the methodological quality and risk of bias of studies included, according to the Cochrane RoB tool. The SYRCLE’s RoB tool assesses 10 items, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases.

Outcomes

Outcomes extracted from the included studies for evaluating the beneficial effects of vanadium were: (1) Inflammatory biomarkers such as TNF-α, interleukin 6 (Il-6), high-sensitivity C-reactive protein (hs-CRP); (2) oxidative stress biomarkers including GSH, SOD, CAT, GPx, glutathione S-transferase (GST), and GR.


Results

Identification of relevant studies

During the electronic search, 2593 potentially eligible studies were identified. Then, reviewing the title and abstract of studies resulted in the exclusion of 2252 studies, due to not fulfilling the inclusion criteria, or being randomized controlled trials or review articles. Afterward, 341 full-text papers were further reviewed. Eventually, 42 studies were eligible for inclusion. A flow diagram outlining the selection of final papers can be observed in . Among the 42 studies included, 40 studies reported the beneficial therapeutic effects of vanadium on the enzymatic activity of inflammatory and oxidative stress biomarkers in diabetes-induced animal studies.

hpp-12-122-g001
Figure 1. Flow diagram outlining included animal studies selection

Characteristics of studies included in the analysis

Table S1 summarizes the characteristics of animal studies included. The studies’ publication dates ranged from August 199037 to November 2021.38 In 24 out of the included studies,12,16-18,20,21,39-56 randomization was reported. Sample size was from 2057 to 902animals. Streptozotocin2,12-14,16-21,37-42,44,45,48-61 or alloxan monohydrate6,8,11,22,24,46,47,62,63 wereused for inducing diabetes, except for one study43 that used high-fat low-sucrose diet for inducing insulin resistance. All of the studies were accomplished on rodents. In 8 studies,38,40,41,44,58,61 Sprague-Dawley rats were used, while in the rest, Swiss Albino of Wistar strain rats were investigated. Additionally, 3 studies2,16,43 were on mice species. Rat’s mean weight was 175 g and mice’s mean weight was 26.5 g. Sources of vanadium consumed for administration were vanadyl sulfate (20 studies),2,12,17,18,21,39-42,44,48-51,53,54,57,58,60 sodium orthovanadate (10 studies),6,8,11,19,22,37,46,62-64 oxovanadium (IV) complex (1 study),2 vanadium pentoxide (2 studies),20 Na[(O2)2(2,2’-bpy)] • 8 H2O vanadium complexes (1 study),13 vanadyl(IV)-ascorbate (VOAsc) complex (1 study),43 dioxidovanadium cis-[VO2(obz)py]) complex (1 study),38 NaVO3 (3 studies),21,47 vanadium-3-hydroxy flavone complex (1 study),59 macrocyclic binuclear oxovanadium (IV) complex (MBOV) (1 study),14 bis(maltolato)oxovanadium (IV) (2 studies),16,45 dioxidovanadium (1 study),61 vanadium citrate (1 study),24 V3dipic-Cl 21 and oxovanadium(IV) chelate [VOL] (1 study).51 Method of administration was either by dissolving into drinking water,6,8,11,16,17,19,21,22,24,37,40,41,44-47,57-59,62,63,65 gavage,12-14,18,20,38,39,42,43,48-54,61 or intraperitoneal injection.60 Duration of the interventions ranged from 15 days up to 60 days. Measured outcomes were the enzymatic activity of inflammatory biomarkers such as TNF-α, Il-6, hs-CRP, caspase 3, as well as oxidative stress biomarkers including GSH, SOD, GPx, GST, and GR.

Quality assessment

Randomization was reported in 24 of the included studies.12,16-18,20,21,39-56 Animals were similar in age and weight and were kept in controlled and similar conditions. illustrates the methodological quality assessment of studies and shows the risk of bias of each item, as percentages.

hpp-12-122-g002
Figure 2. Risk of bias indicating studies’ quality assessment at an individual level. (+ ) Low risk of bias. (-) High risk of bias. (?) Unclear risk of bias

hpp-12-122-g003
Figure 3. Risk of bias of included studies as percentages

Overview of outcome measures

Among the included studies, 18 studies assessed the effectiveness of vanadium on GSH. In all studies, GSH level was significantly increased, except for one study,46 which observed no significant differences. Vanadyl sulfate supplementation significantly enhanced GSH levels in diabetes-induced animals.12,17,18,39,42,49,50,52 Other vanadium complexes such as oxovanadium (IV), Na[(O2)2(2,2’-bpy)] • 8 H2O, Na[VO(O2)2(1,10’-phen)] • 5 H2O, [VO(SO4)(1,10’-phen)] • 2 H2O, vanadyl (IV)-ascorbate (VOAsc), vanadium-3-hydroxy flavone, macrocyclic binuclear oxovanadium (IV) complex (MBOV), sodium orthovanadate, vanadium citrate, vanadium pentoxide, oxovanadium (IV) chelate also augmented GSH level.2,13,14,24,37,43,51,59

Among the studies included, 27 studies analyzed the effectiveness of vanadium on GR, GST, and GPx levels. In one study, vanadium administration was inefficient in enhancing GPx level,46 and in five studies, vanadium administration significantly declined GPx levels.16,42,53,54,63 However, in the remaining of the studies, GPx level was significantly enhanced.6,8,11,14,19-22,24,37,38,43,48,51,59,61 Vanadium administration significantly increased GST level in 7 studies.8,11,17,48,50,57,62 In one study,11 no significant changes were observed. Vanadium administration significantly enhanced GR level in 4 studies.8,11,19,24 No significant changes were observed in one study,42 but a significant decline was observed in two studies.53,54

In addition, 27 studies assessed the effect of vanadium on SOD level out of which 20 observed significant enhancement. Also, in 3 studies, significant alterations were not observed.13,45,46 In five studies, vanadium treatment declined SOD level.16,42,47,53,54 Vanadyl sulfate supplementation could also significantly augment SOD level.2,21,41,42,44,48,50,53,54,60 Other compounds such as oxovanadium (IV) complex, sodium orthovanadate, [VO(SO4)(1,10’-phen)] • 2 H2O, [VO(SO4)(2,2’-bpy)] • H2O, vanadyl(IV)-ascorbate, Dioxidovanadium (V) complex, vanadium-3-hydroxy flavone complex, macrocyclic binuclear oxovanadium (IV) complex, bis(maltolato)oxovanadium IV (BMOV), vanadium citrate, vanadium pentoxide also enhanced SOD level in different tissues of animals.2,6,8,13,14,16,19,20,22,24,37,38,43,46,51,59,63

Among the included studies, 21 assessed the effect of vanadium on CAT levels. In all of the studies, the CAT level significantly increased, except for two studies in which vanadium administration was not efficient8,46 and in 4 studies in which CAT level declined.16,42,45,52 In 6 studies,21,42,48,50,52,60 vanadyl sulfate administration significantly restored the altered enzymatic activity level of CAT to normal level. Sodium orthovanadate, vanadium-3-hydroxy flavone complex, macrocyclic binuclear oxovanadium (IV) complex, bis(maltolato)oxovanadium (IV), vanadium citrate, oxovanadium (IV) chelate were also effective in restoring CAT enzymatic activity level to near normal level in different tissues.6,14,16,19,21,22,24,37,45,46,51,59,63 However, in one study sodium orthovanadate administration was not effective in altering CAT level.8

Inflammatory biomarkers were assessed in 7 studies and significant decline was observed in all studies. Vanadyl sulfate supplementation significantly reduced TNF-α, IL-6, and hs-CRP.40,41,44,58,63 Vanadyl (IV)-ascorbate (VOAsc) complex and dioxidovanadium also reduced these inflammatory biomarkers.43,61 Caspase 3 level significantly decreased after oxovanadium (IV) complex and VOSO4 treatment.66


Discussion

In the present systematic review, most of the studies claimed beneficial features for vanadium concerning inflammatory and oxidative stress biomarkers in their overall conclusion, despite treatment with different compounds of vanadium, doses, species, methods of administration, and length of intervention. In the included studies, impaired enzymes levels expressed as either decrease or increase, were accepted as oxidative stress. For example, in few studies in which antioxidant enzymes were enhanced in the cells for compensating an antioxidant defense during diabetes, vanadium administration was able to restore the number of enzymes impaired.42,53,54 Despite the observed beneficial impact of vanadium compounds in controlling inflammatory and oxidative stress biomarkers, there were few studies that indicated no significant effects.

In Saxena and colleagues’ study, vanadate supplementation was useful in optimizing antioxidant enzymes of diabetes-induced animal models. This was mainly because vanadium in the form of vanadate was able to create different forms of free radicals, or distract the antioxidant system.46 In Gupta and colleagues’ study, no significant changes in the activity of CAT was observed after vanadium treatment. In the study of Krośniak et al, vanadium (V) peroxocomplexes treatment was not efficient regarding SOD level. This may be due to various oxidative positions and organic/inorganic ligands of vanadium (V) peroxocomplexes.13 The increased NAD(P)H: quinone-oxidoreductase-1 activity in diabetic rats may have decreased the formation of ROS, which would explain why no changes in SOD level were observed.45 A recent study claimed that the administration of 1 mg/day BMOV in diabetes-induced animal models was not efficient in declining inflammatory biomarkers.56

As far as we know, the current systematic review was the first to assess the effect of vanadium on inflammatory and oxidative stress biomarkers in diabetes-induced animals. The last publications regarding vanadium and diabetes were mainly regarding glycemic factors.30 Hence, several advantages could be mentioned for the present study. First, it included a high number of animal studies. Second, it assessed various outcomes. Third, it evaluated the effect of various organic and inorganic vanadium forms. Forth, it used the SYRCLE’s risk of bias tool for evaluating the methodological quality of studies. However, few limitations can be mentioned for this systematic review, as below: (1) non-English studies were excluded; (2) gray literatures were not extracted during further searches (3) studies that supplemented vanadium along with insulin and/ or other compounds were also included.


Conclusion

The present systematic review reaffirmed that vanadium compounds in different doses and methods of administration were efficient in normalizing inflammatory and oxidative stress biomarkers in T2DM. Furthermore, addressing high-quality clinical trials for assessing the effectiveness of vanadium is encouraged.


Authors’ contributions

FG and AO were involved in the concept of the manuscript; FG was responsible for writing the draft of the manuscript; MSA reviewed and edited the manuscript; and the final manuscript was read and approved by all of the authors.


Funding

The research protocol was funded by Student Research Committee, Tabriz University of Medical Sciences (grant number: 67836), Tabriz, Iran.


Ethical approval

Not applicable.


Competing interests

No conflict of interest was reported.


Disclaimer

The authors claim that no part of this paper is copied from other sources.


Supplementary Files

Supplementary file 1 contains Table S1.


References

  1. Relationship between oxidative stress, ER stress, and inflammation in type 2 diabetes: the battle continues. J Clin Med 2019; 8(9):1385. doi: 10.3390/jcm8091385 [Crossref]
  2. The role of apoptosis and autophagy in the insulin-enhancing activity of oxovanadium (IV) bipyridine complex in streptozotocin-induced diabetic mice. Biometals 2020; 33(2-3):123-35. doi: 10.1007/s10534-020-00237-1 [Crossref]
  3. Induction of diabetes mellitus in rats using intraperitoneal streptozotocin: a comparison between 2 strains of rats. Eur J Sci Res 2009; 32(3):398-402.
  4. Macrophage-mediated cholesterol handling in atherosclerosis. J Cell Mol Med 2016; 20(1):17-28. doi: 10.1111/jcmm.12689 [Crossref]
  5. New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. Redox Biol 2019; 20:247-60. doi: 10.1016/j.redox.2018.09.025 [Crossref]
  6. Beneficial effects of Trigonella foenum graecum and sodium orthovanadate on metabolic parameters in experimental diabetes. Cell Biochem Funct 2012; 30(6):464-73. doi: 10.1002/cbf.2819 [Crossref]
  7. Vanadium and insulin: partners in metabolic regulation. J Inorg Biochem 2020; 208:111094. doi: 10.1016/j.jinorgbio.2020.111094 [Crossref]
  8. Hexokinase, glucose-6-phosphate dehydrogenase and antioxidant enzymes in diabetic reticulocytes: effects of insulin and vanadate. Biochem Mol Biol Int 1998; 46(6):1145-52. doi: 10.1080/15216549800204702 [Crossref]
  9. Antioxidant enzyme activity and lipid peroxidation in the blood of rats co-treated with vanadium (V + 5) and chromium (Cr + 3). Cell Biol Toxicol 2010; 26(6):509-26. doi: 10.1007/s10565-010-9160-8 [Crossref]
  10. [Impact of green tea on oxidative stress induced by ammonium metavanadate exposure in male rats]. C R Biol 2006; 329(10):775-84. doi: 10.1016/j.crvi.2006.07.004 [Crossref]
  11. Protective effects of sodium orthovanadate in diabetic reticulocytes and ageing red blood cells of Wistar rats. J Biosci 2004; 29(1):73-9. doi: 10.1007/bf02702564 [Crossref]
  12. Effects of vanadyl sulfate on liver of streptozotocin-induced diabetic rats. Biol Trace Elem Res 2005; 104(3):233-47. doi: 10.1385/bter:104:3:233 [Crossref]
  13. Effect of vanadium complexes and insulin administered simultaneously for oxidative stress in STZ diabetic rats. Bull Vet Inst Pulawy 2009; 53(3):535-40. doi: 10.1007/s12011-013-9688-6 [Crossref]
  14. Protective effect of macrocyclic binuclear oxovanadium complex on oxidative stress in pancreas of streptozotocin induced diabetic rats. Chem Biol Interact 2004; 149(1):9-21. doi: 10.1016/j.cbi.2004.06.007 [Crossref]
  15. Effects of sodium-orthovanadate and Trigonella foenum-graecum seeds on hepatic and renal lipogenic enzymes and lipid profile during alloxan diabetes. J Biosci 2004; 29(1):81-91. doi: 10.1007/bf02702565 [Crossref]
  16. Bis (quercetinato) oxovanadium IV reverses metabolic changes in streptozotocin-induced diabetic mice. Rev Diabet Stud 2007; 4(1):33-43. doi: 10.1900/rds.2007.4.33 [Crossref]
  17. Effect of vanadyl sulfate feeding on susceptibility to peroxidative change in diabetic rats. Res Commun Chem Pathol Pharmacol 1993; 80(2):187-200.
  18. Protective effect of vanadyl sulfate on the pancreas of streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2005; 70(2):103-9. doi: 10.1016/j.diabres.2005.02.003 [Crossref]
  19. Effect of lower doses of vanadate in combination with Azadirachta indica leaf extract on hepatic and renal antioxidant enzymes in streptozotocin-induced diabetic rats. Biol Trace Elem Res 2013; 156(1-3):202-9. doi: 10.1007/s12011-013-9827-0 [Crossref]
  20. Antioxidant status in STZ-induced diabetic rats treated with vanadium pentoxide nanoparticles. Indian J Anim Res 2019; 53(12):1594-8. doi: 10.18805/ijar.B-3709 [Crossref]
  21. Effects of vanadium (III, IV, V)-chlorodipicolinate on glycolysis and antioxidant status in the liver of STZ-induced diabetic rats. J Inorg Biochem 2014; 136:47-56. doi: 10.1016/j.jinorgbio.2014.03.011 [Crossref]
  22. Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonellafoenum graecum). Mol Cell Biochem 2002; 236(1-2):7-12. doi: 10.1023/a:1016103131408 [Crossref]
  23. Long-term treatment of diabetic rats with vanadyl sulfate or insulin attenuate acute focal cerebral ischemia/reperfusion injury via their antiglycemic effect. Metab Brain Dis 2018; 33(1):225-35. doi: 10.1007/s11011-017-0153-7 [Crossref]
  24. Glutathione status in rat’s liver experimentally induced under influence chromium citrate. Ukr Biochem J 2018; 90(6):141. doi: 10.15407/ubj90.06 [Crossref]
  25. Effects of vanadate on male rat reproductive tract histology, oxidative stress markers and androgenic enzyme activities. J Inorg Biochem 2007; 101(6):944-56. doi: 10.1016/j.jinorgbio.2007.03.003 [Crossref]
  26. Srivastava AK, Mehdi MZInsulino-mimetic and anti-diabetic effects of vanadium compoundsDiabet. Med 2005; 22(1):2-13. doi: 10.1111/j.1464-5491.2004.01381.x [Crossref]
  27. Diabetes-altered gene expression in rat skeletal muscle corrected by oral administration of vanadyl sulfate. Physiol Genomics 2006; 26(3):192-201. doi: 10.1152/physiolgenomics.00196.2005 [Crossref]
  28. Effect of macrocyclic binuclear oxovanadium complex on tissue defense system in streptozotocin-induced diabetic rats. Clin Chim Acta 2004; 345(1-2):141-50. doi: 10.1016/j.cccn.2004.03.014 [Crossref]
  29. A systematic review of vanadium oral supplements for glycaemic control in type 2 diabetes mellitus. QJM 2008; 101(5):351-8. doi: 10.1093/qjmed/hcn003 [Crossref]
  30. Effects of vanadium compounds on glycemic control in type 2 diabetes mellitus: a meta-analysis of comparative study on rats. Int J Pharm Sci Res 2012; 3(10):3717-24.
  31. A systematic review of systematic reviews and meta-analyses of animal experiments with guidelines for reporting. J Environ Sci Health B 2006; 41(7):1245-58. doi: 10.1080/03601230600857130 [Crossref]
  32. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement (Chinese edition). Chin J Integr Med 2009; 7(9):889-96. doi: 10.3736/jcim20090918 [Crossref]
  33. A step-by-step guide to systematically identify all relevant animal studies. Lab Anim 2012; 46(1):24-31. doi: 10.1258/la.2011.011087 [Crossref]
  34. Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed. Lab Anim 2010; 44(3):170-5. doi: 10.1258/la.2010.009117 [Crossref]
  35. . Cochrane Handbook for Systematic Reviews of Interventions 2019.
  36. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 2014; 14:43. doi: 10.1186/1471-2288-14-43 [Crossref]
  37. Antioxidant effect of vanadate on experimental diabetic rats. Acta Diabetol Lat 1990; 27(4):285-93. doi: 10.1007/bf02580932 [Crossref]
  38. Cardio-protective effects of a dioxidovanadium (V) complex in male Sprague-Dawley rats with streptozotocin-induced diabetes. Biometals 2021; 34(1):161-73. doi: 10.1007/s10534-020-00270-0 [Crossref]
  39. Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta. Cell Biochem Funct 2007; 25(6):603-9. doi: 10.1002/cbf.1354 [Crossref]
  40. [Vanadium inhibits type 2 diabetes mellitus-induced aortic ultrastructural alterations associated with the inhibition of dyslipidemia and biomarkers of inflammation in rats]. Int J Morphol 2020; 38(1):215-21. doi: 10.4067/s0717-95022020000100215 [Crossref]
  41. Insulin and vanadium protect against osteoarthritis development secondary to diabetes mellitus in rats. Arch Physiol Biochem 2016; 122(3):148-54. doi: 10.3109/13813455.2016.1159698 [Crossref]
  42. Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats. Biometals 2011; 24(5):943-9. doi: 10.1007/s10534-011-9452-3 [Crossref]
  43. Ameliorative effect of vanadyl (IV)-ascorbate complex on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice. J Trace Elem Med Biol 2015; 32:155-61. doi: 10.1016/j.jtemb.2015.07.007 [Crossref]
  44. The impact of concomitant administration of vanadium and insulin on endothelial dysfunction markers (PAI-1 and ET-1) in type 1 diabetic rats. Arch Physiol Biochem 2021; 127(1):20-7. doi: 10.1080/13813455.2019.1573840 [Crossref]
  45. Changes in iron metabolism and oxidative status in STZ-induced diabetic rats treated with bis (maltolato) oxovanadium (IV) as an antidiabetic agent. ScientificWorldJournal 2014; 2014:706074. doi: 10.1155/2014/706074 [Crossref]
  46. Saxena AK, Srivastava P, Kale RK, Baquer NZImpaired antioxidant status in diabetic rat liverEffect of vanadate. Biochem Pharmacol 1993; 45(3):539-42. doi: 10.1016/0006-2952(93)90124-f [Crossref]
  47. The protective effect of vanadium against diabetic cataracts in diabetic rat model. Biol Trace Elem Res 2014; 158(2):219-23. doi: 10.1007/s12011-014-9925-7 [Crossref]
  48. Study of the beneficial effect of vanadium sulfate on the liver of experimental diabetic rats. Istanbul J Pharm 2020; 50(3):211-5. doi: 10.26650/IstanbulJPharm.2020.0065 [Crossref]
  49. Effect of vanadyl sulfate on the status of lipid parameters and on stomach and spleen tissues of streptozotocin-induced diabetic rats. Pharmacol Res 2006; 53(3):271-7. doi: 10.1016/j.phrs.2005.12.004 [Crossref]
  50. Protective effect of vanadyl sulfate on skin injury in streptozotocin-induced diabetic rats. Hum Exp Toxicol 2013; 32(11):1206-12. doi: 10.1177/0960327113478445 [Crossref]
  51. Synthesis, characterization and antidiabetic properties of N1-2,4-dihydroxybenzylidene-N4-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium (IV). Eur J Med Chem 2009; 44(2):818-26. doi: 10.1016/j.ejmech.2008.04.023 [Crossref]
  52. Vanadyl sulfate administration protects the streptozotocin-induced oxidative damage to brain tissue in rats. Mol Cell Biochem 2006; 286(1-2):153-9. doi: 10.1007/s11010-005-9107-1 [Crossref]
  53. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats. Bosn J Basic Med Sci 2014; 14(2):105-9. doi: 10.17305/bjbms.2014.2273 [Crossref]
  54. Effect of oral vanadium supplementation on oxidative stress factors in the lung tissue of diabetic rats. Trace Elements Electrolytes 2014; 31(2):48-52. doi: 10.5414/tex01317 [Crossref]
  55. Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats. Metallomics 2012; 4(8):814-9. doi: 10.1039/c2mt20066j [Crossref]
  56. Vanadium decreases hepcidin mRNA gene expression in STZ-induced diabetic rats, improving the anemic state. Nutrients 2021; 13(4):1256. doi: 10.3390/nu13041256 [Crossref]
  57. Diabetes-altered gene expression in rat skeletal muscle corrected by oral administration of vanadyl sulfate. Physiol Genomics 2006; 26(3):192-201. doi: 10.1152/physiolgenomics.00196.2005 [Crossref]
  58. Modulatory effect of concomitant administration of insulin and vanadium on inflammatory biomarkers in type 2 diabetic rats: role of adiponectin. Chin J Physiol 2018; 61(1):42-9. doi: 10.4077/cjp.2018.bag523 [Crossref]
  59. Antidyslipidemic effect of a novel vanadium-3-hydroxy flavone complex in streptozotocin-induced experimental diabetes in rats. Biomed Prev Nutr 2014; 4(2):189-93. doi: 10.1016/j.bionut.2013.04.004 [Crossref]
  60. Hepatotoxicity of vanadyl sulfate in nondiabetic and streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 2018; 96(11):1076-83. doi: 10.1139/cjpp-2018-0255 [Crossref]
  61. The effect of dioxidovanadium complex (V) on hepatic function in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 2019; 97(12):1169-75. doi: 10.1139/cjpp-2019-0369 [Crossref]
  62. Vanadium improves brain acetylcholinesterase activity on early stage alloxan-diabetic rats. Neurosci Lett 2008; 436(1):44-7. doi: 10.1016/j.neulet.2008.02.073 [Crossref]
  63. Amelioration of altered antioxidant status and membrane linked functions by vanadium and Trigonella in alloxan diabetic rat brains. J Biosci 2005; 30(4):483-90. doi: 10.1007/bf02703722 [Crossref]
  64. Sodium orthovanadate and Trigonella foenum graecum prevents neuronal parameters decline and impaired glucose homeostasis in alloxan diabetic rats. Prague Med Rep 2015; 116(2):122-38. doi: 10.14712/23362936.2015.51 [Crossref]
  65. Vanadium treatment of diabetic Sprague-Dawley rats results in tissue vanadium accumulation and pro-oxidant effects. Toxicology 1993; 83(1-3):115-30. doi: 10.1016/0300-483x(93)90096-b [Crossref]
  66. The role of apoptosis and autophagy in the insulin-enhancing activity of oxovanadium (IV) bipyridine complex in streptozotocin-induced diabetic mice. Biometals 2020; 33(2-3):123-35. doi: 10.1007/s10534-020-00237-1 [Crossref]
Submitted: 04 Feb 2022
Accepted: 24 Jul 2022
First published online: 20 Aug 2022
EndNote EndNote

(Enw Format - Win & Mac)

BibTeX BibTeX

(Bib Format - Win & Mac)

Bookends Bookends

(Ris Format - Mac only)

EasyBib EasyBib

(Ris Format - Win & Mac)

Medlars Medlars

(Txt Format - Win & Mac)

Mendeley Web Mendeley Web
Mendeley Mendeley

(Ris Format - Win & Mac)

Papers Papers

(Ris Format - Win & Mac)

ProCite ProCite

(Ris Format - Win & Mac)

Reference Manager Reference Manager

(Ris Format - Win only)

Refworks Refworks

(Refworks Format - Win & Mac)

Zotero Zotero

(Ris Format - FireFox Plugin)

Abstract View: 605
PDF Download: 477
Full Text View: 145