Gastric ulcer - healing promoting activity of cobalt chloride in rats.
Abstract
Background: Gastric ulcer develops when aggressive factors overcome protective factors in the gastrointestinal tract. Cobalt chloride is used in the manufacturing of vitamin B12, essential for folate and fatty acid metabolism. Information regarding probable effects of Cobalt Chloride on Ulcer healing is void despite its vast use which this study addresses.
Method: 70 Male Wistar rats (150-180g, n=10) were used and induced with ulcer using acetic acid (excluding control) before grouping: Groups 1- Control, 2 - ulcer alone, 3 and 4 were ulcerated treated with 62 and 25mg/kg b.w of Cobalt chloride (CoCl2 ); 5, 6 and 7 were ulcerated treated with 1, 40 and 30mg/kg b.w of Misoprostol, Cimetidine and Omeprazole respectively for 2 weeks. Gastric acid secretion, ulcer scores and histopathology of ulcerated areas were evaluated on days 7, 14 and 21. Data were analyzed using ANOVA and considered significant at p<0.05.
Result: This study revealed significant decrease in gastric acid secretion (and pH) of control (0.65±0.02) and treatment groups - high (0.86±0.01) and low (0.85±0.02) CoCl2 compared to ulcer untreated (1.22±0.04) by day 7 post ulceration. A significant decrease in ulcer index of treatment group (high and low CoCl2 ) by day 7(90.18% and 91.21%) respectively and complete healing day 14 was observed. Histological evaluations of CoCl2 treated group revealed intact epithelium with normal glands by days 7 and post ulceration. There was no ulcer reformation in examined stomach, by day 21 (day 7 post 25mg/kg b.w CoCl2 treatment).
Conclusion: Probably, Cobalt chloride exerts its anti-ulcerogenic property by stimulating gastric protective activities.
Keyword: Cobalt chloride, gastric ulcer healing, gastric acidity.
Résumé
Contexte: L’ulcère gastrique se développe lorsque des facteurs agressifs surmontent les facteurs protecteurs du tractus gastro-intestinal. Le chlorure de cobalt est utilisé dans la fabrication de la vitamine B12, essentielle pour le métabolisme des acides foliques et gras. L’information concernant les effets probables du chlorure de cobalt sur la cicatrisation des ulcères est nulle en dépit de son vaste utilisation qui fait l’objet de cette étude.
Méthode : 70 rats Wistar (150-180g, n = 10) ont été utilisés et induits avec un ulcère en utilisant de l’acide acétique (excluant le contrôle) avant le regroupement: groupes 1- contrôle, 2 - ulcère seul, 3 et 4 ulcérés traités avec 62 et 25 mg / kg pc de chlorure de cobalt (CoCl2 ); 5, 6 et 7 ont été traités avec 1, 40 et 30 mg / kg pc de misoprostole, de cimétidine et d’oméprazole respectivement pendant 2 semaines. La sécrétion d’acide gastrique, les scores d’ulcère et l’histopathologie des zones ulcérées ont été évalués aux jours 7, 14 et 21. Les données ont été analysées en utilisant ANOVA et considérées significatives à p <0,05.
Résultat : Cette étude a révélé la diminution significative de la sécrétion d’acide gastrique (et pH) des groupes de contrôle (0,65 ± 0,02) et de traitement - élevé (0,86 ± 0,01) et faible (0,85 ± 0,02)
CoCl2 par rapport au groupe d’ulcère non traité (1,22 ± 0,04) au jour 7 après l’ulcération. Une diminution significative de l’indice d’ulcère du groupe de traitement (CoCl2 élevé et faible) au jour 7 (90,18% et 91,21%) respectivement et la cicatrisation complète jour 14 a été observée. Les évaluations histologiques du groupe traité par CoCl2 ont révélé un épithélium intact avec des glandes normales au jour 7 et postulcération. Il n’y a pas eu de réformation d’ulcère dans les estomacs examinés, au jour 21 (au jour 7 après traitement avec 25 mg / kg pc de CoCl2 ).
Conclusion: Probablement, le chlorure de cobalt exerce sa propriété d’anti-ulcération en stimulant des activités de protection gastrique.
Mot - clé : Chlorure de cobalt, cicatrisation de l’ulcère gastrique, acidité gastrique .
Correspondence: Dr A.T. Salami, Gastrointestinal Secretion and Inflammatory Research Unit, Department of Physiology, University of Ibadan, Ibadan, Nigeria. E-mail: adeolathabitha@yahoo.com
References
Allen A. and Flemström, G. Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. American Journal of Physiology - Cell Physiology. 2005; 288(1): C1–C19, ISSN :1522-1563.
Wallace L. John. Prostaglandins, NSAIDs and Gastric Mucosal Protection: Why doesn’t the stomach digest itself? Physiological Reviews Article. 2008; 88(4):1547 – 1565.
Shaker EH and Mahmoud S. Mnaa Anti-inflammatory and anti-ulcer activity of the extract from Alhagi maurorum (camelthorn) Food and Chemical Toxicology. 2010; 48: 2785–2790.
Forssell H and Olbe L. Continuous computerized determination of gastric bicarbonate secretion in man. Scand J Gastroenterol. 1985; 20: 767-774.
Snowden F. Emerging and reemerging diseases: a historical perspective. Immunol. Rev. 2008; 225(1): 9–26.
Folkmann J, Szabo S, Stovroff M, et al. Duodenal ulcer. Discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg.1991; 241: 414-425.
Goldwasser E, Jacobson LO, Fried W and Plzak LF. Studies on erythropoiesis. V. the effect of cobalt on the production of erythropoietin. Blood. 1958; 13: 55-60.
Davis JE and Fields JP. Experimental production of polycythemia in humans by administration of cobalt chloride. Exp Biol Med. 1958; 99: 493-495.
Bowie EA and Hurley PJ. Cobalt chloride in the treatment of refractory anaemia in patients undergoing long term haemodialysis. Aust N Z J Med. 1975; 5: 306-314.
Duckham JM and Lee HA. The treatment of refractory anaemia of chronic renal failure with cobalt chloride. Q J Med. 1976; 45: 277-294.
Taylor A and Marks V. cobalt: a review. J Hum Nutr. 1978; 32: 165-177.
Tietz NW (ed): Clinical guide to laboratory tests. Philadelphia PA:WA. Saunders co. 1983; pg 129.
Lippi G, Franchini M and Guidi GC. Blood doping by cobalt. Should we measure cobalt in athletes? J Occup Med Toxicol. 2006; 1:18.
Jelkmann W. Efficacy of recombinant erythropoietins: is there unity of of international units? Nephrol Dial Transplant. 2009; 24: 1366- 1368.
Saxena S, Shukla D and Bansal A. Augumentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride. Toxicology and Applied Pharmacology. 2012; 264 (3): 324-334.
Shukla D, Saxena S, Purushothaman J, et al. Hypoxic preconditioning with cobalt ameliorates hypobaric hypoxia induced pulmonary edema in rat. Eur J Pharmacol. 2011;10;656 (1-3):101-109.
Reynolds JEF and Prasad AB (eds). Martindale- The extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press. 1982; p. 1697.
Clarke EG and Clarke ML. Veterniary Toxicology, Baltimore, Maryland: The Williams and Wilkins Company, 1975; p 253.
Yildirum O and Buyukbingol Z. Biol Trace Elem Res. 2002; 90 (1-3): 143-154.
Tephly TR and Hibbeln P. The effect of cobalt chloride administration on the synthesis of hepatic microsomal cytochrome P-450. Biochemical and Biophysical research communications. 1971; 42(4): 589-595.
Schuster BE.; Roszell LE.; Murr LE. et al. In vivo corrosion, tumor outcome, and microarray gene expression for two types of muscle-implanted tungsten alloys. / In: Toxicology and Applied Pharmacology. 2012; 265(1): 128-138.
Miller AC and McClain D. A review of depleted uranium biological effects: in vitro and in vivo studies. Rev Environ Health. 2007; 22: 75–89
Simonsen LO, Harbak H and Bennekou P. Cobalt metabolism and toxicology—a brief update. Sci Total Environ. 2012; 432: 210-215.
Finley BL, Monnot AD, Paustenbach DJ and Gaffney SH.: Derivation of a chronic oral reference dose for cobalt. Regul Toxicol Pharmacol. 2012; 64: 491-503.
Carson BL, Ellis HV and MCCann JL. Toxicology and Biological Monitoring of metals in humans. Lewis Publisher Inc. Michigan USA. 1986.
Campbell J R and Estey MP. Metal release from hip prostheses: cobalt and chromium toxicity and the role of the clinical laboratory. Clin Chem Lab Med. 2013; 51(1):213-220.
Matthew GP, William ED, Thomas ES, et al. Stallings. Exposure to Cobalt Causes Transcriptomic and Proteomic Changes in Two Rat Liver Derived Cell Lines. PLoS One. 2013; 8(12):e83751.
Motohashi H and Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med. 2004; 10: 549–557.
Alexander CS. Cobalt-beer cardiomyopathy. A clinical and pathologic study of twenty-eight cases. AM J Med. 1972; 53:395-417.
EEFA Panel on Additives and Products or Subtances used in Animal Feed (FEEDAP), Scientific Opinion on the use of cobalt compounds as additives in animal nutrition. EFSA Journal. 2009; 7(12): 1383.
Kaptan K, Beyan C, Ural AU, et al. Helicobacter pylori—is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med. 2000; 160(9):1349-1353.
Jelkmann W. The disparate roles of cobalt in erythropoiesis and doping relevance. Open journal of haematology. 2012; (3): 6.
Ghosh MN and Schild HO. Continuous recording of acid gastric secretion in the rat. Br. J. Pharm. 1958; 13: 54-61.
Amure BO and Ginsburg M. Inhibitors of histamine catabolism and the action of gastrin in the rat. Br J Pharmacology Chemotherapy. 1964; 23: 476 -485.
Umamaheswari M, Asokkumar K, Rathidevi R, et al. Antiulcer and in vitro antioxidant activities of Jasminum grandiflorum L. Journal of Ethnopharmacology. 2007; 110: 464–470.
Okabe S and Pfeifler CJ. Chronicity of Acetic Acid Ulcer in the Rat Stomach. Digestions Diseases. 1972; 17: 619.
Jainu M, Srinivasulu C and Devi S. Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental ulcer models: Possible mechanism for the inhibition of acid formation. Journal of Ethnopharmacology. 2006; 104: 156–163.
Okabe S, Kikuko A and Koji T. Acetic acid ulcer model - state of the art in 2010. Gastroenterologia Polska. 2010; 17(3): 165 – 168.
Samuel A, Singh Neetu, Olaleye Samuel B.,et al. Anti- ulcer & antioxidant activities of Hedranthera barteri {(Hook F.) Pichon} with possible involvement of H+, K+.ATPase inhibitory activity.Indian J Med Res. 2010; 132: 442- 449.
Salami AT, Ndukauba NG Iyiola TO, et al. Gastroprotective Properties of Manganese Chloride on Acetic Acid Induced Ulcer In Wistar Rats. Afr. J. Biomed. Res. 2014; 17: 109 - 117.
Jainu M, Mohan KV and Devi CSS. Gastrorotective effect of Cissus quadrangularis extract in rats with experimentally induced ulcer. Indian J Med Res. 2006; 123: 799–806
Takagi K, Okabe S. and Saziki R. “A new method for the production of Chronic gastric ulcer in rats and the effect of several drugs on its healing,” Japanese Journal of Pharmacology, 1970; 19(3): 418–421.
Okabe S and K. Amagase. “An overview of acetic acid ulcer models: the history and state of the art of peptic ulcer research,” Biological and Pharmaceutical Bulletin. 2005; 28(8): 1321–1341.
Tulassay Z and Herszenyi L. Gatsric mucosal defense and cytoprotection. Best Practice and Research Clinical Gastroenterology. 2010; 24(2): 99-101.
Hollander, F. The two-component mucous barrier. Archives of Iniernal Medicine. 1954; 93: 107-120.
Ho SB, Takamura K , Anway R , et al. The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins. Dig Dis Sci. 2004; 49: 1598- 606.
Domschke W., Domschke S, Hagel J, Demling L and Croft DN. Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone. Gut. 1977; 18: 817-820.