title: Diabetes enhances lipopolysaccharide-induced cardiac toxicity in the mouse model.
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-alpha (TNF-alpha) 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-alpha and IL-6 concentrations. Diabetes did not alter the effect of lipopolysaccharide on serum and cardiac TNF-alpha elevation, but it significantly enhanced lipopolysaccharideinduced cardiac IL-6 production. These results suggest that diabetes significantly enhances endotoxin-induced cardiac toxicity, possibly through mechanisms that involve inflammatory/acute-phase cytokines.
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Song
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D018805:Sepsis / Q000139:chemically induced / Q000209:etiology; D014280:Triglycerides / Q000097:blood; D020107:Troponin T / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014280:Triglycerides; D020107:Troponin T; D014409:Tumor Necrosis Factor-alpha; D003402:Creatine Kinase