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Effect of a Novel Molybdenum Ascorbate Complex on Ex Vivo Myocardial Performance in Chemical Diabetes Mellitus

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Abstract

Background: The insulin-like action of metal complexes on target tissues, including the heart, has been reported in experimental diabetes mellitus. Since streptozotocin-induced diabetes is associated with insulin deficiency and left ventricular dysfunction, this study was designed to determine whether the novel metal complex molybdenum ascorbate [MoO2(aa)2] would improve cardiac function in this model of diabetes.

Methods: Diabetes was induced in Sprague-Dawley rats (n = 6) following an intravenous injection of streptozotocin (60 mg/kg). After 8 weeks of diabetes, cardiac function was determined in isolated working hearts perfused with 11 mmol/L glucose, 1.2 mmol/L palmitate and 3% albumin. MoO2(aa)2 was added directly into the perfusate of working hearts at a concentration of 200 μmol/L for a period of 30 minutes. Age-matched control rats served as controls (n = 6).

Results: Cardiac function, expressed as heart rate (HR) and aortic flow, was significantly decreased in diabetic hearts compared with control hearts. The diabetic state was associated with 23% and 60% reductions in HR and aortic flow, respectively. Short-term addition of MoO2(aa)2 was beneficial and partially prevented the attenuation in diabetic rat heart function. MoO2(aa)2 increased HR by 15%, while aortic flow was increased by 85%. In control hearts, MoO2(aa)2 had no effect on HR and increased aortic flow by 12%.

Conclusion: This study extends previous observations on the benefit of metal complexes in experimental diabetes. Our results indicate that short-term treatment with MoO2(aa)2 partially reversed the left ventricular dysfunction associated with the streptozotocin model of diabetes.

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Acknowledgements

Thanks are extended to the Heart and Stroke Foundation of New Brunswick (TLB & SAW), Mount Allison University (SAW), the Natural Science and Engineering Research Council (Canada), the Canada Research Chairs Program, and the Canadian Foundation for Innovation/Atlantic Innovation Fund. We also thank Dan Durant (MAU) and Roger Smith (MAU) for expert technical assistance. The authors have no financial interests or other conflicts of interest relevant to the content of this study.

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Authors and Affiliations

  1. Department of Physiology, Midwestern University, 19555 North 59th Avenue, Glendale, Arizona, 85308, USA

    Tom L. Broderick

  2. Department of Biology, Mount Allison University, Sackville, New Brunswick, Canada

    John Bailey

  3. Department of Chemistry, Mount Allison University, Sackville, New Brunswick, Canada

    Karen J. Gagnon, Sarah J. Lord, Christopher M. Vogels & Stephen A. Westcott

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  1. Tom L. Broderick
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  2. John Bailey
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  3. Karen J. Gagnon
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  4. Sarah J. Lord
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  5. Christopher M. Vogels
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  6. Stephen A. Westcott
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Correspondence to Tom L. Broderick.

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Broderick, T.L., Bailey, J., Gagnon, K.J. et al. Effect of a Novel Molybdenum Ascorbate Complex on Ex Vivo Myocardial Performance in Chemical Diabetes Mellitus. Drugs R D 7, 119–125 (2006). https://doi.org/10.2165/00126839-200607020-00006

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  • DOI: https://doi.org/10.2165/00126839-200607020-00006

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