Abstract | BACKGROUND: METHODS: Twenty leptin receptor null (db/db) mice underwent treatment with TAD (1 mg/Kg) or 10% DMSO for 28 days. Body weight and fasting plasma glucose levels were determined weekly. Upon completion, hearts were isolated and subjected to 30 min global ischemia followed by 60 min reperfusion in a Langendorff model. Plasma samples were taken for cytokine analysis and fasting triglyceride levels. Infarct size was measured using computer morphometry of tetrazolium stained sections. Additionally, ventricular cardiomyocytes were isolated and subjected to 40 min of simulated ischemia and reoxygenation. Necrosis was determined using trypan blue exclusion and LDH release assay and apoptosis was assessed by TUNEL assay after 1 h or 18 h of reoxygenation, respectively. RESULTS: Treatment with TAD caused a reduction in infarct size in the diabetic heart (23.2 ± 1.5 vs. 47.8 ± 3.7%, p<0.01, n = 6/group), reduced fasting glucose levels (292 ± 31.8 vs. 511 ± 19.3 mg/dL, p<0.001) and fasting triglycerides (43.3 ± 21 vs. 129.7 ± 29 mg/dL, p<0.05) as compared to DMSO, however body weight was not significantly reduced. Circulating tumor necrosis factor-α and interleukin-1β were reduced after treatment compared to control (257 ± 16.51 vs. 402.3 ± 17.26 and 150.8 ± 12.55 vs. 264 ± 31.85 pg/mL, respectively; P<0.001) Isolated cardiomyocytes from TAD-treated mice showed reduced apoptosis and necrosis. CONCLUSION:
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Authors | Amit Varma, Anindita Das, Nicholas N Hoke, David E Durrant, Fadi N Salloum, Rakesh C Kukreja |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 9
Pg. e45243
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23028874
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Carbolines
- Interleukin-1beta
- Phosphodiesterase Inhibitors
- Receptors, Leptin
- Triglycerides
- Tumor Necrosis Factor-alpha
- leptin receptor, mouse
- Tadalafil
- Cyclic Nucleotide Phosphodiesterases, Type 5
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Topics |
- Animals
- Apoptosis
(drug effects)
- Blood Glucose
(metabolism)
- Body Weight
(drug effects)
- Carbolines
(pharmacology, therapeutic use)
- Cyclic Nucleotide Phosphodiesterases, Type 5
(metabolism)
- Diabetes Mellitus, Experimental
(complications, drug therapy, metabolism)
- Drug Administration Schedule
- Fasting
- Interleukin-1beta
(blood)
- Male
- Mice
- Mice, Knockout
- Myocardial Infarction
(complications, drug therapy, metabolism)
- Myocardial Reperfusion Injury
(complications, drug therapy, metabolism)
- Myocytes, Cardiac
(drug effects, metabolism)
- Necrosis
(complications, drug therapy, metabolism)
- Obesity
(complications, drug therapy, metabolism)
- Phosphodiesterase Inhibitors
(pharmacology, therapeutic use)
- Receptors, Leptin
(genetics)
- Tadalafil
- Triglycerides
(blood)
- Tumor Necrosis Factor-alpha
(blood)
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