Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs in R&D
Published in: Drugs in R&D 1/2006

01-01-2006 | Original Research Article

A Newly Synthesised Molybdenum/Ascorbic Acid Complex Alleviates Some Effects of Cardiomyopathy in Streptozocin-Induced Diabetic Rats

Authors: K. MacDonald, Dr J. Bailey, C. MacRory, C. Friis, C. M. Vogels, T. Broderick, S. A. Westcott

Published in: Drugs in R&D | Issue 1/2006

Login to get access

Abstract

Background: Exogenous insulin does not prevent cardiac failure in patients with type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed. Certain transition metals are known to act as insulin mimics and may be cardioprotective. In this study, the ability of a newly synthesised molybdenum/ascorbic acid complex to strengthen cardiac function was investigated.
Methods and design: Male CD rats were assigned to one of five groups: non-diabetic control, non-diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated with sodium ascorbate, diabetic treated with molybdenum/ ascorbic acid complex and untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once diabetes was confirmed, treatment was initiated by adding either the molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and continued for 6 weeks. Following the treatment period, the animals were terminated, and their hearts were excised and mounted in a working heart perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid level determination. Cardiac function was evaluated using 1 hour of low-flow ischaemic stress followed by 30 minutes of reperfusion.
Results: Hearts from the animals treated with the molybdenum/ascorbic acid complex displayed the best aerobic performance of all the diabetic animals. Blood glucose levels and blood lipid levels were significantly lower in animals treated with the complex than in other diabetic animals. The group treated with the complex also had a lower drinking rate than the other diabetic groups. Furthermore, hearts from animals treated with the molybdenum/ascorbic acid complex showed a greater degree of recovery from low-flow ischaemia than any other group.
Conclusions: The molybdenum/ascorbic acid complex showed some significant insulin-mimic and cardioprotective effects. Further development of this complex could provide a drug useful for alleviating some of the cardiovascular problems associated with diabetes mellitus.
Literature
1.
Hadley ME. Endocrinology. 4th ed. Upper Saddle River (NJ): Prentice Hall, 1982
2.
Youngren JF, Goldfine ID. The molecular basis of insulin resistance. Science and Medicine, 1997 May/Jun; 18–27
3.
Brichard S, Henquin JC. The role of vanadium in the management of diabetes. Trends Pharmacol Sci 1995; 16: 265–70PubMedCrossRef
4.
Guyton CG, Hall JE. Textbook of medical physiology. 9th ed. Philadelphia (PA): WB Saunders Company, 1996
5.
Lopaschuk GD. Abnormal mechanical function in diabetes: relationship to altered myocardial carbohydrate/lipid metabolism. Coron Artery Dis 1996; 7: 116–23PubMedCrossRef
6.
Trueblood N, Ramasamy R. Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts. Am J Physiol 1998; 275 (1 Pt 2): H75–83PubMed
7.
Dhalla NS, Pierce GN, Innes IR, et al. Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J Cardiol 1985; 1: 263–81PubMed
8.
Yuen VG, Orvig C, Thompson KH, et al. Improvement in cardiac dysfunction in streptozocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovandium (IV). Can J Physiol Pharmacol 1992; 71: 270–6CrossRef
9.
Thompson KH, McNeill JH, Orvig C. Vanadium compounds as insulin mimics. Chem Rev 1999; 99: 2561–71PubMedCrossRef
10.
11.
Ozcelikay AT, Becker DJ, Ongemba LN, et al. Improvement of glucose and lipid metabolism in diabetic rats treated with molybdate. Am J Physiol 1996; 270: E344–52PubMed
12.
Fillat C, Rodriguez-Gil JE, Guinovart JJ. Molybdate and tung- state act like vanadate on glucose metabolism in isolated hepatocytes. Biochem J 1992; 282: 659–63PubMed
13.
Lord SJ, Epstein NA, Paddock RL, et al. Synthesis, characterization, and biological relevance of hydroxypyron and hydroxypyridinone complexes of molybdenum. Can J Chem 1999; 77: 1249–61CrossRef
14.
Singh RB, Mohammad NA, Agarwal P, et al. Effect of antioxidant-rich foods on plasma ascorbic acid, cardiac enzyme and lipid peroxide levels in patients hospitalized with acute myocardial infarction. J Am Diabet Assoc 1995; 95: 775–83CrossRef
15.
Munson M, Lee Y. Natural nitro? Prevention; Emmaus 1996; 48: 25
16.
Nyyssonen K, Parviainen MT, Salonen R, et al. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 1997; 314 (7081): 634–8PubMedCrossRef
17.
Dai S, McNeill JH. Ascorbic acid supplementation prevents hyperlipidemia and improves myocardial performance in streptozocin-diabetic rats. Diabet Res Clin Pract 1995; 27: 11–8CrossRef
18.
Nicholl TA, Lopaschuk GD, McNeill JH. Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. Am J Physiol 1991; 266: H1053–9
19.
Broderick TL, Quinney HA, Lopaschuk GD. L-carnitine increases glucose metabolism and mechanical function following ischaemia in diabetic rat heart. Cardiovasc Res 1995; 29: 373–8PubMed
20.
Gamble J, Lopaschuk GD. Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats. Biochim Biophys Acta 1994; 1225: 191–4PubMedCrossRef
21.
Maddaford TG, Russell JC, Pierce GN. Postischemic cardiac performance in the insulin resistant JCR: LA-cp rat. Am J Physiol 1997; 273: H1187–92PubMed
22.
Rodrigues B, Goyal RK, McNeill JH. Effects of hydralazine on streptozotocin-induced diabetic rats: prevention of hyperlipidemia and improvement in cardiac function. J Pharmacol Exp Ther 1986; 237: 292–9PubMed
23.
Liedtke AJ, Nellis SH, Mjos OD. Effects of reducing fatty acid metabolism on mechanical function in regionally ischemic hearts. Am J Physiol 1983; 247: H387–94
24.
Wall SR, Lopaschuk GD. Glucose oxidation rates in fatty acid-perfused isolated working hearts from diabetic rats. Biochem Biophys Acta 1989; 10006: 97–103
25.
Neely JR, Morgan HE. Relationship between carbohydrate metabolism and energy balance of heart muscle. Ann Rev Physiol 1974; 36: 413–59CrossRef
Metadata
Title
A Newly Synthesised Molybdenum/Ascorbic Acid Complex Alleviates Some Effects of Cardiomyopathy in Streptozocin-Induced Diabetic Rats
Authors
K. MacDonald
Dr J. Bailey
C. MacRory
C. Friis
C. M. Vogels
T. Broderick
S. A. Westcott
Publication date
01-01-2006
Publisher
Springer International Publishing
Published in
Drugs in R&D / Issue 1/2006
Print ISSN: 1174-5886
Electronic ISSN: 1179-6901
DOI
https://doi.org/10.2165/00126839-200607010-00003

Other articles of this Issue 1/2006

Drugs in R&D 1/2006 Go to the issue

Adis R&D Profile

Tipranavir

Review Article

The Role of Intracellular Calcium Signals in Inflammatory Responses of Polarised Cystic Fibrosis Human Airway Epithelia

Original Research Article

Effect of Dexmedetomidine on Haemodynamic Responses to Laryngoscopy and Intubation

Review Article

Targeting Virulence for Antibacterial Chemotherapy