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Abstract
Vanadium, a heavy metal with insulin-mimetic properties and gastro-protective potentials, has been reported to protect the stomach of healthy rats against aggressive agents like acetic acid. In this study, we investigated the gastroprotective effects of low-dose sodium metavanadate (NaVO₃) in experimental diabetic rats. One hundred male Wistar rats (100-130g) were randomized into two experiments (normal and diseased) with 5 major groups (n=10) each. First experiment included normal (control) and non-diabetic groups treated with varying doses (20mg/kg/p.o, 40mg/kg/p.o, 60mg/kg/p.o and 80mg/kg/p.o) of sodium metavanadate (NaVO3) only. The second experiment included diabetes-induced (65mg/kg/i.p Streptozotocin-STZ) and diabetic groups concomitantly treated with the same doses of sodium metavanadate as in the first experiment. Body weight and blood glucose level (BGL) were measured weekly. After 8 weeks of treatment, gastric acid secretion (GAS) was determined by the continuous perfusion method. Gastric tissue malondialdehyde (MDA), reduced glutathione (GSH), sulfhydryl, nitric oxide levels, Na+/K+ and H+-K+-ATPase pump activities were assessed spectrophotometrically. Gastric tissue histological examination and immunohistochemistry expression of gastric MUC5AC were evaluated. Data were analyzed using two-way ANOVA and were significant at p < 0.05. The BGL was significantly decreased in 20 and 40 mg/kg NaVO₃-treated groups in both non-diabetic and diabetic Wistar groups. Basal GAS significantly decreased in NaVO3-treated diabetic groups. Stimulation with acetylcholine significantly decreased GAS in NaVO3-non-diabetic treated groups. Gastric MDA and GSH were significantly reduced in 60 and 80mg/kg-NaVO3 non-diabetic treated groups. Gastric sulfhydryl and nitric oxide levels were significantly reduced in 20 and 40mg/kg-NaVO3 non-diabetic treated groups. Treatment with NaVO₃ in diabetic groups significantly decreased gastric MDA and sulfhydryl but increased GSH and nitric oxide levels. Gastric H+- K+ ATPase and Na+-K+ ATPase pump activities significantly decreased in diabetic groups treated with 20, 40 and 60mg/kg-NaVO3 compared with the untreated diabetes group. Gastric MUC5AC expression in NaVO₃ non-diabetic and NaVO₃-treated diabetic groups significantly increased compared with control and diabetes alone, respectively. Sodium metavanadate treatment dose-dependently reduced blood glucose levels and improved body weight in diabetic rats. It also modulated gastric acid secretion via the suppression of H⁺/K⁺-ATPase and Na⁺/K⁺-ATPase activities, reduced oxidative stress markers, enhanced antioxidant defences, and increased expression of gastric MUC5AC
References
Adam, A. M. A., Naglah, A. M., Al-Omar, M. A., and Refat, M. S. (2017) : Synthesis of a new insulin-mimetic anti-diabetic drug containing vitamin A and vanadium(IV) salt: Chemico-biological characterizations. International Journal of Immunopathology and Pharmacology, 30(3), 272–281.
Amure BO, Ginsburg M (1964): Inhibitors of Histamine catabolism and the action of gastrin in the rat. Br J Pharmacol Chemother; 23:476-485.
Balali-Mood Mahdi, Naseri Kobra, Tahergorabi Zoya, Khazdair Mohammad Reza, Sadeghi Mahmood (2021): Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic, Frontiers in Pharmacology, volume 12
Battle W. M., Snape W. J. Jr, Alavi A., Cohen S. and Braunstein S. (1980): Colonic dysfunction in diabetes mellitus. Gastroenterology 79, 1217-1221
Bech K. (1986): Effect of somatostatin on histaminestimulated gastric acid secretion in dogs. Scand. J. Gastroenterol. 21, 662-668.
Brichard SM, Bailey CJ and Henquin J-C (1990): Marked improvement of glucose homeostasis in diabetic ob / ob mice given oral vanadate.Diabetes 39: 1326–1332
Burghen GA, Murrell LR, Whitington CL, Klyce MK, Burstein S (1992): Acid peptic disease in children with type 1 diabetes mellitus. Am J Dis Child; 146:718–722
Chang, F. Y., Chen, T. S., Lee, S. D., Yeh, G. H., Doong, M. L., & Wang, P. S. (2002): Acid-inhibitory potency of ranitidine in diabetic rats. Pharmacology, 66(1), 5–10.
Dayanand, Y., Pather, R., Xulu, N., Booysen, I., Sibiya, N., Khathi, A., & Ngubane, P. (2024): Exploring the Biological Effects of Anti-Diabetic Vanadium Compounds in the Liver, Heart and Brain. Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3267–3278. https://doi.org/10.2147/DMSO.S417700
De Block CEM, De Leeuw IH, Pelckmans PA (2002): Delayed gastric empyting and gastric motility in type1 diabetes. Care; 25 (5): 912 – 917.
Desai H. G. (1969): Factors affecting maximal acid secretion. Postgraduate medical journal, 45(522), 272–278.
Domingo, J. L., and Gómez, M. (2016): Vanadium compounds for the treatment of human diabetes mellitus: A scientific curiosity? A review of thirty years of research. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association, 95, 137–141.
Forte J. G. and Yao X. (1996): The membrane-recruitment-and-recycling hypothesis of gastric HCl secretion. Trends Cell Biol. 6, 45–48.
Furness, J. B., Di Natale, M., Hunne, B., Oparija-Rogenmozere, L., Ward, S. M., Sasse, K. C., Powley, T. L., Stebbing, M. J., Jaffey, D., and Fothergill, L. J. (2020): The identification of neuronal control pathways supplying effector tissues in the stomach. Cell and tissue research, 382(3), 433–445.
Gilbert, T.T, Olaolorun, F.A, LadaguA.D, Olopade, F.E, Igado, O. and Olopade J.O (2023): Neurobehavioural and Histological Study of the Effects of Low-Dose and High-Dose Vanadium in Brain, Liver and Kidney of Mice. Nigerian Journal of Physiological Sciences, 38(1), 47-56. https://doi.org/10.54548/njps.v38i1.8
Ghosh MN and Schild HO (1958): A method for continous recording of gastric secretion in the rat. Am J Physiol; 128:35-6
Jaishankar, M., Tseten, T., Anbalagan, N., Mathew, B. B., & Beeregowda, K. N. (2014): Toxicity, mechanism and health effects of some heavy metals. Interdisciplinary toxicology, 7(2), 60–72.
Kim, J., Chun, S., Ohk, S. O., Kim, S., Kim, J., Lee, S., Kim, H., & Kim, S. (2021): Amelioration of alcohol induced gastric mucosa damage by oral administration of food polydeoxyribonucleotides. Molecular medicine reports, 24(5), 790.
Lin, C. Y., Yeh, G. H., Hsu, F. C., Tsai, S. C., Lau, C. P., Pu, H. F., Yu, H. L., Tung, Y. F., & Wang, P. S. (1991): Gastric acid secretion in streptozotocin-diabetic female rats. The Chinese journal of physiology, 34(2), 179–186.
Meyerovitch, J., Rothenberg, P., Shechter, Y., Bonner-Weir, S., & Kahn, C. R. (1991): Vanadate normalizes hyperglycemia in two mouse models of non-insulin-dependent diabetes mellitus. The Journal of clinical investigation, 87(4), 1286–1294.
Omayone, T.P., Salami, A.T., Oluwole, F.S. and Olaleye, S.B. (2016): Gastroprotective effect of vanadium in rats: roles of gastric acid and nitric oxide. J. Afr. Ass. Physiol. Sci.; 4(1): 32-40.
Ozcelikay VM, Altan YM, Yildizoglu-Ari N, Altinkurt O, Onur F, Ozturk Y (1993): Basal and histamine-induced gastric acid secretion in alloxan diabetic rats. Gen Pharmacol; 24(1): 121- 126.
Prinz, C., Kajimura, M., Scott, D., Helander, H., Shin, J., Besancon, M., Bamberg, K., Hersey, S., & Sachs, G. (1992): Acid secretion and the H+K+ATPase of stomach. The Yale journal of biology and medicine, 65(6), 577–596.
Schubert M and Peura D (2008): Control of Gastric Acid Secretion in Health and Disease _ 10.1053_j.gastro.2008.05.021
Schubert, M. L., & Shamburek, R. D. (1990): Control of acid secretion. Gastroenterology clinics of North America, 19(1), 1–25.
Sirchak Y. S., Barani V. Y., Odoshevska O. M., Petrichko O. I. (2021): Peculiarities of Determining the Gastric Acid Secretion and Diabetic Autonomic Neuropathy in Patients with Chronic Pancreatitis and Type 2 Diabetes. Wiad Lek; 74(4):981-985. DOI: 10.36740/WLek202104132
Suthar, P.B., Jain, S.M., Mehta, A.A., and Santani, D.D. (2007): Study of anti-ulcer activity of sodium metavanadate on alcohol and pylorus ligation induced gastric ulcers in rats. Ind J Pharmaceutical Sciences. 69(3): 454-6
Szelenyi, I.and Vergin, H. (1980). Cholinergic Pathway of Gastric Acid Secretion in the Isolated Whole Stomach of the Mouse. Pharmacology, 21(4), 268–276
Takeuchi K, Ueshima K, Ohuchi T, Okabe S (1994): Induction of gastric lesions and hypoglycemic response by food deprivation in streptozotocindiabetic rats. Dig Dis Sci; 39:626–634.
Tashima K, Nishijima M, Fujita A, Kubomi M, Takeuchi K: Acid secretory changes in streptozotocin-diabetic rats (2000): Different responses to various secretagogues. Dig Dis Sci; 45: 1352–1358.
Treviño, S., Díaz, A., Sánchez-Lara, E., Sanchez-Gaytan, B. L., Perez-Aguilar, J. M., & González-Vergara, E. (2019): Vanadium in Biological Action: Chemical, Pharmacological Aspects, and Metabolic Implications in Diabetes Mellitus. Biological trace element research, 188(1), 68–98.
Trinder, P. (1966): Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem. 6:24
Yao, X., & Forte, J. G. (2003): Cell biology of acid secretion by the parietal cell. Annual review of physiology, 65, 103–131.
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