Cardiovascular Toxicology

, Volume 3, Issue 4, pp 363–372

Diabetes enhances lipopolysaccharide-induced cardiac toxicity in the mouse model

Authors

  • Ye Song
    • Department of MedicineUniversity of Louisville School of Medicine
  • Zhenyuan Song
    • Department of MedicineUniversity of Louisville School of Medicine
  • Li Zhang
    • Department of MedicineUniversity of Louisville School of Medicine
  • Craig J. McClain
    • Department of MedicineUniversity of Louisville School of Medicine
    • Department of Pharmacology & ToxicologyUniversity of Louisville School of Medicine
    • Veterans Administration
  • Y. James Kang
    • Department of MedicineUniversity of Louisville School of Medicine
    • Department of Pharmacology & ToxicologyUniversity of Louisville School of Medicine
    • Jewish Hospital Heart and Lung Institute
    • Department of MedicineUniversity of Louisville School of Medicine
Article

DOI: 10.1385/CT:3:4:363

Cite this article as:
Song, Y., Song, Z., Zhang, L. et al. Cardiovasc Toxicol (2003) 3: 363. doi:10.1385/CT:3:4:363

Abstract

Diabetic patients have a higher rate of mortality from sepsis than do their nondiabetic septic counterparts. The hypothesis in this study is that chronic diabetes may make cardiovascular systems more sensitive to septicemia. To test this hypothesis, the authors investigated the effect of diabetes on endotoxin-induced cardiac toxicity. Diabetes was induced in FVB mice by injecting a single dose (150 mg/kg) of streptozotocin. Two months after streptozotocin treatment, the diabetic mice were treated with lipopolysaccharide by intraperitoneal injection at 2 mg/kg. Cardiac toxicity was evaluated by measuring levels of serum cardiac enzymes and cardiac morphology at 1 h, 4.5 h, and 24 h after lipopolysaccharide treatment. Serum and cardiac tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay methods at 1 h and 4.5 h after lipopolysaccharide treatment. Lipopolysaccharide treatment did not significantly affect the diabetic manifestations, including decreased body weight gain and increased glycated hemoglobin and serum triglyceride levels. However, diabetes significantly enhanced lipopolysaccharide-induced cardiac toxicity, which was demonstrated by significant increases in the levels of cardiac enzymes such as creatine phosphokinase and troponin T, abnormal morphological changes examined under light microscope with hematoxylin and eosin staining, and oxidative damage to proteins detected by 3-nitrotyrosine staining. Lipopolysaccharide treatment significantly increased serum and cardiac TNF-α and IL-6 concentrations. Diabetes did not alter the effect of lipopolysaccharide on serum and cardiac TNF-α elevation, but it significantly enhanced lipopolysaccharide-induced cardiac IL-6 production. These results suggest that diabetes significantly enhances endotoxin-induced cardiac toxicity, possibly through mechanisms that involve inflammatory/acute-phase cytokines.

Key Words

Diabetic cardiotoxicity endotoxin mouse troponin T cytokines inflammatory factors tumor necrosis factor-α interleukin-6

Copyright information

© Humana Press Inc 2003