Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts

AbstractObjective: It has recently been proposed that nitric oxide synthase, in the presence of suboptimal levels of tetrahydrobiopterin, an essential cofactor of this enzyme, might favor increased production of oxygen radicals. The aim of this study was to clarify whether supplement with tetrahydrobiopterin would exert a cardioprotective effect against ischemia-reperfusion injury. Methods: Isolated perfused rat hearts were subjected to 30 minutes of global ischemia and 30 minutes of reperfusion at 37°C. Hearts were treated with tetrahydrobiopterin or vehicle for 5 minutes just before ischemia and during the first 5 minutes of the reperfusion period. Effects of tetrahydrobiopterin on left ventricular function, myocardial contents of lipid peroxidation and high-energy phosphates, and levels of lactate dehydrogenase and nitrite plus nitrate in perfusate during ischemia and after reperfusion were estimated and further compared with those of superoxide dismutase plus catalase or l-ascorbic acid. Results: Tetrahydrobiopterin and superoxide dismutase plus catalase both improved contractile and metabolic abnormalities in reperfused hearts. On the other hand, l-ascorbic acid at a dose having an equipotent radical scavenging activity with tetrahydrobiopterin did not significantly affect the postischemic changes. Although tetrahydrobiopterin and superoxide dismutase plus catalase significantly alleviated ischemic contracture during ischemia, diminished perfusate levels of nitrite plus nitrate after reperfusion were restored only with tetrahydrobiopterin. Conclusion: Results demonstrated that tetrahydrobiopterin lessens ischemia-reperfusion injury in isolated perfused rat hearts, probably independent of its intrinsic radical scavenging action. The cardioprotective effect of tetrahydrobiopterin implies that tetrahydrobiopterin could be a novel and effective therapeutic option in the treatment of ischemia-reperfusion injury.J Thorac Cardiovasc Surg 2002;124:775-8

Protective effect of Actinidia arguta in MPTP-induced Parkinson’s disease model mice

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress-induced neuronal death has been identified as one of the major causes of nigrostriatal degeneration in PD. The fruit of Actinidia arguta (A. arguta), known as sarunashi in Japan, has been reported to show beneficial health effects such as antioxidant, anti-inflammatory, anti-mutagenic, and anticholinergic effects. In this study, we investigated the neuroprotective effects of A. arguta in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-induced PD model mice. A. arguta juice was administered to 7-week-old C57BL/6J mice continuously for 10 days before the first MPTP injection. The degeneration of dopaminergic neurons in the substantia nigra was induced by MPTP (30 mg/kg, i. p.) once daily for five consecutive days. We found that the administration of A. arguta ameliorated MPTP-induced motor impairment and suppressed the MPTP-induced reductions of tyrosine hydroxylase-positive neurons and tyrosine hydroxylase protein expression in the substantia nigra. Our findings suggest that taking A. arguta could provide neuroprotection that delays or prevents the neurodegenerative process of PD

Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits

1. Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. 2. Rabbits were given with EPO (400 iu kg(−1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I(2) were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. 3. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(−1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(−1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I(2) were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. 4. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. 5. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. 6. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase