GENOTOXIC AND CYTOTOXIC EFFECTS OF ORAL VANADYL SULPHATE
AbstractBackground: Vanadyl sulphate is available as herbal medicine against diabetes mellitus and body building supplement, over the counter worldwide. The available data on its safety is controversial and inadequate. The objective of this study was to analyse its safety in usual therapeutic dose range. Methods: It was an experimental study carried out at the Department of Biochemistry & Molecular Biology, Army Medical College, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from Jun 2014 to Oct 2018. The study was carried out on 105 Sprague Dawley rats for a duration of 24 weeks. The animals were randomly distributed in three groups of 35 each. The group I rats were marked as control while rats of group II & III were administered vanadyl sulphate 0.06mg/day and 0.3mg/day respectively. Alanine amino transferase (ALT) and Malondialdehyde (MDA) were measured in serum while comet assay was performed on WBCs. Results: The plasma levels of ALT and MDA were significantly raised in group II and III subjects. Single cell gel electrophoresis (SCGE) / comet assay showed minimal “tail moment” in control group and increased tail moment in group II and III in a dose dependent manner which indicates dsDNA breaks. Conclusion: It was observed that vanadyl sulphate causes hepatocellular toxicity, oxidative stress and damage to the DNA in usual therapeutic/ supplemental doses. Due to hazardous effects, its use in humans as alternate medicine may be reviewed.Keywords: Vanadyl sulphate; Hepatotoxicity; Oxidative Stress; DNA Damage; Comet Assay
Vanadium (vanadyl sulfate). Monograph. Altern Med Rev 2009;14(2):177–80.
Bin-Jaliah I, Sakr HF, Morsy MD, Dallak M, Haidara MA. 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.
Noutsopoulos D, Markopoulos G, Koliou M, Dova L, Vartholomatos G, Kolettas E, et al. Vanadium induces VL30 retrotransposition at an unusually high level: a possible carcinogenesis mechanism. J Mol Biol 2007;374(1):80–90.
Voulgaridou GP, Anestopoulos I, Franco R, Panayiotidis MI, Pappa A. DNA damage induced by endogenous aldehydes: Current state of knowledge. Mutat Res 2011;711(1-2):13–27.
Barrio DA, Etcheverry SB. Potential use of vanadium compounds in therapeutics. Curr Med Chem 2010;17(31):3632–42.
Roy S, Banerjee S, Chakraborty T. Vanadium quercetin complex attenuates mammary cancer by regulating the P53, Akt/mTOR pathway and downregulates cellular proliferation correlated with increased apoptotic events. Biometals 2018;31(4):647–74.
El-Shaari FA, Haider SS, El-Fakhri MM, Ghawarsha KM. Does ascorbic acid protect against vanadium neurotoxicity in different regions of rat brain? Neurosciences (Riyadh) 2002;7(4):278–86.
Cervantes-Yepez S, Lopez-Zepeda LS, Fortoul TI. Vanadium inhalation induces retinal Muller glial cell (MGC) alterations in a murine model. Cutan Ocul Toxicol 2018;37(2):200–6.
Liu X, Cui HM, Peng X, Fang J, Cui W, Wu B. The Effect of Dietary Vanadium on Cell Cycle and Apoptosis of Liver in Broilers. Biol Trace Elem Res 2011;143(3):1508–15.
Villani P, Cordelli E, Leopardi P, Siniscalchi E, Veschetti E, Fresegna AM, et al. Evaluation of genotoxicity of oral exposure to tetravalent vanadium in vivo. Toxicol Lett 2007;170(1):11–8.
Shrivastava S, Jadon A, Shukla S, Mathur R. Reversal of vanadium-induced toxicity by combination therapy of tiferron and alpha-tocopherol in rat during pregnancy and their fetuses. Therapie 2012;67(2):173–82.
Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 1996;45(9):1130–5.
Hussain Shah ZS, Naveed AK, Rashid A. Effects of oral vanadium on glycaemic and lipid profile in rats. J Pak Med Assoc 2016;66(12):1592–6.
Falk M, Lukasova E, Kozubek S. Higher-order chromatin structure in DSB induction, repair and misrepair. Mutat Res 2010;704(1-3):88–100.
Vorob'eva N, Boeva OV, Osipov AN, Bozhenko VK. [Radiation-induced DNA double-stranded breaks and the dynamics of apoptotic death of human peripheral lymphocytes]. Vestn Rentgenol Radiol 2008(4-6):50–4.
Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175(1):184–91.
Shrivastava S, Jadon A, Shukla S, Mathur R. Chelation therapy and vanadium: effect on reproductive organs in rats. Indian J Exp Biol 2007;45(6):515–23.
Altamirano-Lozano MA, Alvarez-Barrera L, Mateos-Nava RA, Fortoul TI, Rodriguez-Mercado JJ. Potential for genotoxic and reprotoxic effects of vanadium compounds due to occupational and environmental exposures: An article based on a presentation at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology, Washington DC, August 15-18, 2012. J Immunotoxicol 2014;11(1):19–27.
Zhang W, Yang T, Li W, Li G, Jiao K. Rapid and sensitive electrochemical sensing of DNA damage induced by V2O5 nanobelts/HCl/H2O2 system in natural dsDNA layer-by-layer films. Biosens Bioelectron 2010;25(10):2370–4.
El-Shenawy NS, Refat MS, Fakihi FH. Decreasing the diabetic complication by vanadyl(VO)2+/vitamin B 6 complex in alloxan-induced diabetic mice. J Mater Sci Mater Med 2013;24(4):911–30.
Kurt O, Ozden TY, Ozsoy N, Tunali S, Can A, Akev N, et al. Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats. Biometals 2011;24(5):943–9.
Tunali S, Yanardag R. 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.
Romero A, Ramos E, de Los Rios C, Egea J, Del Pino J, Reiter RJ. A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res 2014;56(4):343–70.
Scibior A, Zaporowska H, Ostrowski J, Banach A. Combined effect of vanadium(V) and chromium(III) on lipid peroxidation in liver and kidney of rats. Chem Biol Interact 2006;159(3):213–22.
Scibior A, Zaporowska H, Ostrowski J. Selected haematological and biochemical parameters of blood in rats after subchronic administration of vanadium and/or magnesium in drinking water. Arch Environ Contam Toxicol 2006;51(2):287–95.
Kim AD, Zhang R, Kang KA, You HJ, Hyun JW. Increased glutathione synthesis following nrf2 activation by vanadyl sulfate in human chang liver cells. Int J Mol Sci 2011;12(12):8878–94.
Saad SY, Najjar TA. Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on cyclosporine A-induced nephrotoxicity in rats. Arch Toxicol 2005;79(9):493–9.
Ahmadi F, Nematbakhsh M, Kargarfard M, Eshraghi-Jazi F, Talebi A, Shirdavani S. Effect of aerobic exercise against vanadyl sulphate-induced nephrotoxicity and hepatotoxicity in rats. J Renal Inj Prev 2016;5(4):183–7.
Liu Y, Chen DD, Xing YH, Ge N, Zhang Y, Liu J, et al. A new oxovanadium complex enhances renal function by improving insulin signaling pathway in diabetic mice. J Diabetes Complications 2014;28(3):265–72.
Soumya RS, Reshmi R, Jomon S, Antu KA, Riya MP, Raghu KG. Synthesis, characterization and evaluation of the antioxidant potential of vanadium encapsulated guar gum nanoparticles. Food Funct 2014;5(3):535–44.
Leon IE, Butenko N, Di Virgilio AL, Muglia CI, Baran EJ, Cavaco I, et al. Vanadium and cancer treatment: Antitumoral mechanisms of three oxidovanadium(IV) complexes on a human osteosarcoma cell line. J Inorg Biochem 2014;134:106–17.
Ajeawung NF, Faure R, Jones C, Kamnasaran D. Preclinical evaluation of dipotassium bisperoxo (picolinato) oxovanadate V for the treatment of pediatric low-grade gliomas. Future Oncol 2013;9(8):1215–29.
Patra S, Chatterjee S, Si TK, Mukherjea KK. Synthesis, structural characterization, VHPO mimicking peroxidative bromination and DNA nuclease activity of oxovanadium(V) complexes. Dalton Trans 2013;42(37):13425–35.
Leon IE, Di Virgilio AL, Porro V, Muglia CI, Naso LG, Williams PA, et al. Antitumor properties of a vanadyl(IV) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: the role of oxidative stress and apoptosis. Dalton Trans 2013;42(33):11868–80.
Rehder D. Vanadium. Its role for humans. Met Ions Life Sci 2013;13:139–69.
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