Abstract
It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (α1) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal α1-Na, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of α1-Na, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal α1-Na, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.
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Korbeck, J., Baranoska-Bosiacka, I., Gutowka, I. and Chlubek, D. (2012) Biochemical and medical importance of vanadium compounds. Acta Biochim. Pol., 59, 195–200.
Chlubek, D. (2015) The role of vanadium in biology. Metallomics, 7, 730–742.
Dafnis, E. and Sabatini, S. (1994) Biochemistry and pathophysiology of vanadium. Nephron, 67, 133–143.
Sitprija, V. and Eiam-Ong, S. (1998) Vanadium and metabolic problems in Vanadium in the Environment. Part 2: Health Effects (Nriagu, J. Ed.). John Wiley & Sons, Chicago, pp. 91–120.
Dafnis, E., Spohn, M., Lonis, B., Kurtzman, N.A. and Sabatini, S. (1992) Vanadate causes hypokalemic distal renal tubular acidosis. Am. J. Physiol. Renal Physiol., 262, F449–F453.
Cantley, L.C., Josephson, L., Warner, R., Yanagisan, M., Lechene, C. and Guidotti, G. (1977) Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. J. Bio. Chem., 252, 7421–7423.
Clough, L.D. (1985) Inhibition of rat cardiac and renal Na,K-ATPase by high sodium concentrations and vanadate. Life Sci., 37, 799–807.
Grantham, J.J. and Glyn, I.M. (1979) Renal Na,K-ATPase determinants of inhibition by vanadium. Am. J. Physiol. Renal Physiol., 236, F530–F535.
Boscolo, P., Carmingnani, M., Volpe, A.R., Felaco, M. and Giuliano, G. (1994) Renal toxicity and arterial hypertension in rats chronically exposed to vanadate. Occup. Environ. Med., 51, 500–503.
Donaldson, J., Hemming, R. and LaBella, F. (1985) Vanaduim exposure enhances lipid peroxidation in the kidney of rats and mice. Can. J. Physiol. Pharmacol., 63, 196–199.
Mahmoud, K.E., Shalahmetova, T., Deraz, S. and Umbayev, B. (2011) Combined effect of vanadium and nickel on lipid peroxidation and selected parameters of antioxidant system in liver and kidney of male rat. Afr. J. Biotechnol., 10, 18319–18325.
Russanov, E., Zaporowska, H., Ivancheva, E., Kirkova, M. and Konstantinova, S. (1994) Lipid peroxidation and antioxidant enzymes in vanadate-treated rats. Comp. Biochem. Physiol. Pharmacol. Toxicol. Endocrinol., 107, 415–421.
Al-Bayati, M.A., Giri, S.N., Raabe, O.G., Rosenblatt, L.S. and Shifrine, M. (1989) Time and dose-response study of the effects of vanadate on rats: morphological and biochemical changes in organs. J. Environ. Pathol. Toxicol. Oncol., 9, 435–455.
Krawietz, W., Werdan, K. and Erdmann, E. (1980) Stimulation of human cardiac adenylate cyclase by vanadate. Basic Res. Cardiol., 75, 433–437.
Hackbarth, I., Schmitz, W., Scholz, H., Wetzel, E., Erdmann, E., Krawietz, W. and Philipp, G. (1980) Stimulatory effects of vanadate on cyclic AMP levels in cat papillary muscle. Biochem. Pharmacol., 29, 1429–1432.
Schmitz, W., Hackbarth, I., Scholz, H. and Wetzel, E. (1980) Effects of vanadate on the c-AMP system of the heart. Basic Res. Cardiol., 75, 438–443.
Satoh, T., Cohen, H.T. and Katz, A.I. (1992) Intracellular signaling in the regulation of renal Na-K-ATPase. I. Role of cyclic AMP and phospholipase A2. J. Clin. Invest., 89, 1496–1500.
Eiam-Ong, S., Sinphitukkul, K., Manotham, K. and Eiam-Ong, S. (2013) Rapid nongenomic action of aldosterone on protein expressions of Hsp90(α and β) and pc-Src in rat kidney. BioMed Res. Int., 2013, 346480.
Eiam-Ong, S., Sinphitukkul, K., Manotham, K. and Eiam-Ong, S. (2014) Rapid action of aldosterone on protein expressions of protein kinase C alpha and alpha1 sodium potassium adenosine triphosphatase in rat kidney. J. Steroids. Horm. Sci., 5, 125.
Eiam-Ong, S., Chaipipat, M., Manotham, K. and Eiam-Ong, S. (2017) Rapid action of aldosterone on protein levels of sodium-hydrogen exchangers and protein kinase C-beta Iso-forms in rat kidney. Int. J. Endocrinol., 2017, 2975853.
Eiam-Ong, S., Jerawatana, R., Kittikowit, W., Mannontarat, R., Tirawatnapong, T. and Eiam-Ong, S. (2009) Effect of vanadate and potassium depletion on renal H, K-ATPase protein expression. Asian Biomed., 3, 517–523.
Seujang, Y., Kittikowit, W., Eiam-Ong, S. and Eiam-Ong, S. (2006) Lipid peroxidation and renal injury in ischemic reperfusion: Effect of angiotensin inhibition. J. Med. Assoc. Thai., 89, 1686–1693.
Son, J.Y., Kang, Y.J., Kim, K.S., Kim, T.H., Lim, S.K., Lim, H.J., Jeong, T.C., Choi, D.W., Chung, K.H., Lee, B.M. and Kim, H.S. (2014) Evaluation of renal toxicity by combination exposure to melamine and cyanuric acid in male sprague-dawley rats. Toxicol. Res., 30, 99–107.
Tria, E., Luly, P., Tomasi, V., Trevisani, A. and Barnabei, O. (1974) Modulation by cyclic AMP in vitro of liver plasma membrane Na-K-ATPase and protein kinases. Biochim. Biophysic. Acta, 343, 297–306.
Lingham, R.B. and Sen, A.K. (1982) Regulation of rat brain Na+-K+-ATPase activity by cyclic AMP. Biochim. Biophysic. Acta, 688, 475–485.
Fisone, G., Chang, S.X., Nairn, A.C., Czernik, A.J., Hemmings, H.C., Hoog, J.O., Bertorello, A.M., Kaiser, R. and Bergman, T. (1994) Identification of the phosphorylation site for cAMP-dependent protein kinase on Na, K-ATPase and effects of site-directed mutagenesis. J. Biol. Chem., 269, 9368–9373.
Kiroytcheva, M., Cheval, L., Carranza, M., Martin, P., Favre, H., Doucet, A. and Ferailie, E. (1999) Effect of cAMP on the activity and the phosphorylation of Na, K-ATPase in rat thick ascending limb of Henle. Kidney Int., 55, 1819–1831.
Aperia, A., Fryckstedt, J., Svensson, L., Hemmings, H.C. and Nairn, A. (1991) Phosphorylated Mr 32,000 dopamine-and cAMP-regulated phosphoprotein inhibits Na, K-ATPase activity in renal tubule cells. Proc. Natl. Acad. Sci. U.S.A., 88, 2798–2801.
Grantham, J.J. (1980) The renal sodium pump and vana-date. Am. J. Physiol. Renal Physiol., 239, F97–F106.
Phillips, T.D., Nechay, B.R. and Heidelbaugh, N.D. (1983) Vanadium: chemistry and the kidney. Fed. Proc., 42, 2969–2973.
Montes, M.R., Monti, J.L. and Rossi, R.C. (2012) E2-> E1 transition and Rb+ release induced by Na+/K+-ATPase. Vana-date as a tool to investigate the interaction between Rb+ and E2. Biochim. Biophysic. Acta, 1818, 2087–2093.
Higashi, Y. and Bello-Reuss, E. (1980) Effects of sodium orthovanadate on whole kidney and single nephron function. Kidney Int., 18, 302–308.
Soussi, A., Abdennabi, R., Ghorbel, F., Murat, J.C. and El Feki, A.F. (2017) Ameliorated effects of (−)-epigallocate-chin gallate against toxicity induced by vanadium in the kidneys of Wistar rats. Biol. Trace Elem. Res., 180, 239–245.
de la Torre, A., Granero, S., Mayayo, E., Corbella, J. and Domingo, J.L. (1999) Effect of age on vanadium nephrotoxicity in rats. Toxicol. Lett., 105, 75–82.
Scibior, A., Zaporowska, H. and Niedwiecka, I. (2010) Lipid peroxidation in the kidney of rats treated with V and/or Mg in drinking water. J. Appl. Toxicol., 30, 487–496.
Scibior, A., Zaporowska, H., Ostrowski, J. and Banach, A. (2006) Combined effect of vanadium (V) and chromium (III) on lipid peroxidation in liver and kidney of rats. Chem. Biol. Interact., 159, 213–222.
Stern, A., Yin, X., Tsang, S.S., Davison, A. and Moon, J. (1993) Vanaduim as a modulator of cellular regulatory cascades and oncogene expression. Biochem. Cell Biol., 71, 103–112.
Stacey, N.H. and Klassen, C.D. (1981) Comparison of the effects of metals in cellular injury and lipid peroxidation in isolated rat hepatocytes. J. Toxicol. Environ. Health, 7, 139–147.
Liochev, S. and Fridovich, I. (1989) Vanadate-stimulated oxidation of NAD(P)H. Free Rad. Biol. Med., 6, 617–522.
Liochev, S. and Fridovich, I. (1990) Vanadate-stimulated oxidation of NAD(P)H in the presence of biological membranes and other sources of O−2. Archs. Biochem. Biophys., 279, 1–7.
Stankiewicz, P.J., Stern, A. and Davidson, A.J. (1991) Oxidation of NADH by vanadium: kinetics, effects of ligands and role of H2O2 or O2. Archs. Biochem. Biophys., 287, 8–17.
Capella, L.S., Gefe, M.R., Silva, E.F., Mitidieri, O.A., Lopes, A.G., Rumjanek, V.M. and Capella, M.A. (2002) Mechnisms of vanadate-induced cellular toxicity: role of cellular glutathione and NADPH. Arch. Biochem. Biophys., 406, 65–72.
Shi, X., Jiang, H., Mao, Y., Ye, J. and Saffinotti, U. (1996) Vanadium (IV) mediated free radical generation and related 2’-deoxyguanosine hydroxylation and DNA damage. Toxicology, 106, 27–38.
Faller, L.D., Rabon, E. and Sachs, G. (1983) Vanadate binding to the gastric H, K-ATPase and inhibition of the enzyme’s catalytic and transport activities. Biochemistry, 22, 4676–4685.
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Eiam-Ong, S., Nakchui, Y., Chaipipat, M. et al. Vanadate-Induced Renal cAMP and Malondialdehyde Accumulation Suppresses Alpha 1 Sodium Potassium Adenosine Triphosphatase Protein Levels. Toxicol Res. 34, 143–150 (2018). https://doi.org/10.5487/TR.2018.34.2.143
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DOI: https://doi.org/10.5487/TR.2018.34.2.143