Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.

OBJECTIVE: Inflammation-mediated elastin destruction in the aortic medial layer is related to progression of abdominal aortic aneurysm (AAA). Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols, reportedly increases elastin synthesis in vitro and may possess anti-inflammatory effects. We used a rat model to investigate whether EGCG could prevent AAA progression. METHODS: AAA was induced with administration of intraluminal elastase and extraluminal CaCl2 in male rats. Rats were randomly divided into a control group (n = 30) and an EGCG group (n = 30). In the EGCG group, an EGCG solution (20 mg/d) was administered orally to each rat from 2 weeks before AAA induction and continued 4 weeks beyond induction. RESULTS: The abdominal aortic diameter was significantly smaller in the EGCG group than in the control group on day 28 (2.9 ± 0.2 vs 2.3 ± 0.1 mm; P < .0001). The medial layer wall thickness and elastin content were significantly greater in the EGCG group than in the control group on day 28 (68.4 ± 13.6 vs 46.7 ± 13.4 µm [P < .001] and 20.3 ± 4.6 vs 9.5 ± 3.6% [P < .0001], respectively). Gene expression levels of tropoelastin and lysyl oxidase were significantly higher in the EGCG group immediately before AAA induction, indicating promoted elastoregeneration by EGCG administration (tropoelastin: 0.59 ± 0.36 control vs 1.24 ± 0.36 EGCG [P < .05], lysyl oxidase: 0.77 ± 0.45 control vs 1.34 ± 0.4 EGCG [P < .05]) (fold increase). Gene expression levels of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, were significantly downregulated in the EGCG group (1.82 ± 0.71 vs 0.97 ± 0.59 [P < .05] and 3.91 ± 3.24 vs 0.89 ± 0.59 [P < .05], respectively). On day 7, gene expression levels and gelatinolytic activity of matrix metalloproteinase 9 were significantly lower in the EGCG group (1.41 ± 0.86 vs 0.51 ± 0.42 [P < .05] and 1.00 ± 0.17 vs 0.29 ± 0.12 [P < .0001], respectively), whereas gene expression levels of tissue inhibitors of metalloproteinase-1 were significantly higher in the EGCG group (0.96 ± 0.11 vs 1.14 ± 0.09; P < .05). CONCLUSIONS: EGCG attenuated AAA progression in a rat model by preserving the aortic thickness and elastin content of the medial layer through regeneration of elastin, as mediated by anti-inflammatory effects, and subsequent reduction of matrix metalloproteinase activity.

Green Tea Polyphenol Prevents Diabetic Rats From Acute Kidney Injury After Cardiopulmonary Bypass.

BACKGROUND: Acute kidney injury (AKI) is a common complication accompanying cardiopulmonary bypass (CPB) and is independently associated with increased morbidity and death. Diabetes mellitus increases the risk for AKI after CPB. Epigallocatechin-3-gallate (EGCG) is a major component of the polyphenolic fraction of green tea, which possesses cardioprotective activities, as previously reported. We hypothesized that EGCG also possesses a renoprotective effect through its diverse biochemical properties and assessed the effect on renal function after CPB for diabetic rats. METHODS: Goto-Kakizaki rats developing type 2 diabetes mellitus were randomly assigned to one of the following groups: sham (n = 10), CPB (CPB alone, n = 9), or EGCG (CPB + EGCG, n = 10). CPB was conducted for 30 minutes at a flow rate of 100 mL/kg/min in the CPB and EGCG groups. Rats assigned to the EGCG group were administrated EGCG solution orally for 2 weeks before CPB. We evaluated renal biochemical or histologic changes at 24 hours after CPB. RESULTS: Compared with the CPB group, the EGCG group exhibited milder tubular injury histologically (p < 0.0001) and reduced expression of kidney injury molecule-1, a biomarker for renal tubular injury (p < 0.0001) and 8-hydroxy-2'-deoxyguanosine (p < 0.01), indicating attenuated oxidant stress. CONCLUSIONS: Preoperative oral administration of EGCG ameliorates AKI in a CPB model of diabetic rats through antioxidative properties. This simple method could be applied in a clinical setting as a prophylactic renal protection against AKI after CPB, especially for high-risk patients with diabetes mellitus.

Topical application of a biodegradable disc with amiodarone for atrial fibrillation.

BACKGROUND: Amiodarone is a potent anti-atrial fibrillation (AF) agent; however, its systemic administration induces serious side effects such as interstitial pneumonia. To avoid such effects, we developed a local sustained-release system for amiodarone. METHODS: A biodegradable, cross-linkable dextran disc was developed as a sustained-release carrier for amiodarone. Under general anesthesia, Japanese white rabbits underwent median sternotomy and the biodegradable disc with or without amiodarone (30 mg) was implanted onto the surface of the right atrium. Three days after implantation, we measured tissue amiodarone concentrations (n = 5), the AF threshold, and the atrial effective refractory period of the left atrium by using the Langendorff apparatus. The incidences of induced AF evoked by rapid pacing were measured and compared. RESULTS: The right atrial concentration of amiodarone was far higher than that in the lungs, ventricles, or other organs (p < 0.01). The blood concentration of amiodarone was below detectable levels. The amiodarone biodegradable disc significantly increased the AF threshold (amiodarone group, 6.9 ± 4.6 mA versus control group, 0.5 ± 0.6 mA; p < 0.01) and the effective refractory period (amiodarone group, 53.9 ± 8.9 milliseconds versus control group, 43.9 ± 9.5 milliseconds; p = 0.035) of the left atrium, indicating the electrophysiologic effect of the amiodarone biodegradable disc on the left atrium. Further, the amiodarone group was significantly less likely to experience AF, as compared with the control group (p < 0.01). CONCLUSIONS: This approach may be a less invasive and effective therapeutic option for preventing postoperative AF.