• Nutrition Research and Practice
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• v.8 no.3
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• pp.284-291
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• 2014

BACKGROUND/OBJECTIVES: The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis. MATERIALS/METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS: The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-, ${\alpha}$, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION: These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.1
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• pp.40-43
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• 2000

Pyrrolidinedithiocarbamate (PDTC) and N-Acetylcysteine (NAC) are metal and nonmetal-chelating antioxidant which can induce rat and human smooth muscle cell death. When the smooth muscle cells from mouse aorta (MASMC) that we successfully cultured recently was exposed to PDTC and NAC in a normal serum state, the cells were induced to death by these compounds. However, PDTC did not induce the cell death in a serum depleted medium. This data suggests that certain factors in the serum may mediate the cytotoxic effect of PDTC. The metal chelator, Ca-EDTA blocked PDTC-induced cell death, but Cu-, Fe-, and Zn-EDTA did not block the PDTC-induced cell death. This data indicated that copper, iron, and zinc in the serum may lead to the cytotoxic effect of PDTC. Investigation of the intracellular zinc level in PDTC-induced smooth muscle cell death using the zinc probe dye N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide shows that only the muscle-containing layers of the arteries have higher level of zinc. As expected, PDTC increased the intracellular fluorescence level of the zinc. In agreement with these results, the addition of an exogenous metal, zinc, induced the vascular aortic smooth muscle cell death which led to an increased intracellular zinc level. We concluded that PDTC induced mouse aortic smooth muscle cell death required not only zinc level but also intracellular copper and iron level. The mechanism of this antioxidant to induce vascular smooth muscle cell death may provide a new strategy to prevent their proliferation in arteriosclerotic lesions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.743-748
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• 2005

This study was performed for the investigation of vasodilatory efficacy and its underlying mechanisms of Jagumhuan(JGH), a herbal remedy. JGH produced completely endothelium-dependent relaxation and relaxed phenylephrine(PE)-precontracted aorta in a concentration dependent manner. The magnitude of relaxation was greater in PE induced contraction than that of KCl, suggesting involvement of $K^+$ channel in the relaxant effect. Both glibenclamide$(10^{-5}M)$, a $K_{ATP}$ channel inhibitor and indometacin, a cyclooxygenase inhibitor, completely prevented this relaxation. The relaxation effects of JGH, involve in part the release of nitric oxide from the endothelium as pretreatment with L-NAME, an NOS inhibitor, and methylene blue, a cGMP inhibitor, attenuated the responses by 62% and 58%, respectively. In addition, nitrite was produced by JGH in human aortic smooth muscle cells and human umbilical vein endothelial cells. The relaxant effect of JGH was also inhibited by 55.41% by tetraethylammonium(TEA; 5mM), a $K_{Ca}$ channel inhibitor. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with JGH significantly reduced the contraction by PE, suggesting that the relaxant action of the JGH includes inhibition of $Ca^{2+}$ release from intracellular stores. These results indicate that in rat thoracic aorta, JGH may induce vasodilation through ATP sensitive $K^+$ channel activation by prostacyclin production. However, the relaxant effect of JGH may also mediated in part by NO pathways and $Ca^{2+}$ activated $K^+$ channel.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.1
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• pp.39-45
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• 2003

Reactive oxygen species (ROS) have been suggested to be contributory factors in complications of diabetes mellitus. In the present study, we investigated the generation of superoxide, the lipid peroxide level measured as thiobarbituric acid reactive substances, the vasorelaxation of isolated thoracic aorta and the iNOS expression in kidney of streptozotocin induced diabetic rats. Sprague Dawley rats were divided into four groups: control, ascorbate (400 mg/kg rat weight daily in drinking water), diabetic (single dose of 50 mg of STZ/kg i.p.) and diabetic simultaneously fed with ascorbate for 12 wk. Rats in groups were studied at tri-weekly intervals (0 to 12 wk). Diabetic rats were evaluated periodically with changes of plasma glucose levels and body weight. The ascorbate supplimentation attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. In the present experimental condition, the ascorbate supplimentation had no significant effect on plasma glucose levels and changes in body weight of normal rate. The superoxide generation, formation of thiobarbituric acid reactive substance and iNOS expression in kidney were significantly increased in STZ-treated rats that were decreased by ascorbate supplimentation. The ascorbate supplimentation had no effect on vasorelaxation of isolated thoracic aorta. These results indicate that ascorbate supplimentation may exert an inhibitory effect on STZ-induced oxidative tissue damage through protection of pancreatic islet cells by scavanging reactive oxygen species. The ascorbate supplimentation may possibly attenuate the renal complication of diabetes mellitus.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.189-195
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• 2007

To study the protective effects of antioxidants on the radiation damages of the cells, vascular smooth muscle cells(VSMC) from thoracic aorta of Sprague-Dawley rats were cultured and irradiated with gamma-ray. Cell viability was measured by direct cell counting and MTT assay, and flow cytometry was performed to measure fractional distributions of the cells. Gamma-ray irradiation inhibited cell proliferations accompanied with decreased G1 phase and increased S- and G2/M phases, and the maximum effects were observed at 1500 or 2000 cGy. Submaximal concentrations of antioxidants, such as allopurinol, vitamin C, N-acetylcycteine(NAC), lipoic acid, dihydrolipoic acid and rebamipide tended to increase the cell viability suppressed by low dose of radiation(500 cGy), and enalapril and vitamin E increased it significantly. Allopurinol, vitamin E, NAC, lipoic acid, captopril and enalapril significantly increased G1 phase. Allopurinol and vitamin E tended to increase c-Myc expression, detected by Western blot, that was reduced by the radiation, and enalapril increased it significantly. The cell viability and c-Myc expression were highly correlated(r=0.97) with each other. These results suggest that antioxidants, especially enalapril and vitamin E, recover the viability of VSMC from gamma-radiation injury, through a mechanism which includes increase of c-Myc protein expression.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.990-997
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• 2006

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine ($1\;{\mu}M$) and aminophylline ($10\;{\mu}M$) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high $K^{+}$ (80 mM) and phenylephrine ($PE,\;1\;{\mu}M$)-induced contractions, indicating a possible $Ca^{++}$ channel blocking (CCB) effect. When tested against PE ($1\;{\mu}M$) control peaks in normal $Ca^{++}\;and\;Ca^{++}$-free Kreb's solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in $Ca^{++}$-free Kreb's solution, thus indicating specific blockade of $Ca^{++}$ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible $Ca^{++}$ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this $Ca^{++}$ channel blocking effect.

• Journal of Nutrition and Health
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• v.22 no.4
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• pp.237-246
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• 1989

The objective of this study was to determine the metabolic effect of exogenous insulin on Sprague-Dawley rats. In a short-term study, the rats were injected insulin and sacrificed at 0.50, 1, 1.5, 2, 4 and 6hr, respectively. Another group of the rats were injected long-acting insulin everyday and sacrificed at 0, 10, 20 and 30days, respectively. Levels of hemoglobin, hematocrit, plasma glucose, plasma protein, plasma albmin, plasma lipids, cholesterol were determined for each experimental group. Also microscopic observation of fat infiltration of liver and aorta performed. No significant abnormality was abserved either at the short-term or at the long-term insulin injection on normal rats.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.160-165
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• 2019

Objectives: The aim of this study was to evaluate the effect of Ribes khorasanicum (R. khorasanicum); a plant growing in north Khorasan of Iran; on cardiovascular and stress oxidative in acute hypertension induced by N-nitro-l-arginine methyl ester (L-NAME), anitric oxide synthase inhibitor. Methods: Rats were divided into Control, L-NAME (10 mg/kg), Sodium Nitroprusside (SNP) (50 mg/kg) + L-NAME and three treated groups with R. khorasanicum (4, 12 and 24 mg/kg) groups + L-NAME. L-NAME and SNP were injected intravenously and extract intraperitoneal. In R. khorasanicum groups, L-NAME was injected 30 min after injection of the extract. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) were recorded continuously using power lab software. At the end of study oxidative stress parameters including of total thiol content (SH), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in heart and aorta of all groups were also measured. Results: In groups 4 and 24 mg/kg extract +L-NAME, there was a non-significant decrease in SBP and MAP compared to L-NAME group but dose 12 mg/kg significantly attenuate the effect of L-NAME(P < 0.05). In L-NAME group the heart and aorta tissues antioxidant enzymes levels decreased, while in treated rats these enzymes significantly increased. Conclusion: The extract of R. khorasanicum in dose 12 mg/kg show anti-hypertensive effect that is mediated by an effect on NO system or antioxidant parameters.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.135-144
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• 1990

The vascular responses to the vasoactive drugs were evaluated using aortic ring preparations obtained from propylthiouracil (PTU)-treated rats. The body weights and the levels of serum thyroxine $(T{_4})$ and triiodothyronine $(T{_3})$ were significantly decreased in propylthiouracil-treated rats as compared with those in age-matched control rats. The contractile responses to norepinephrine and potassium and calcium ions were significantly attenuated in aortic rings of PTU-treated rats 4 weeks after when compared with those from age-matched control animals. By the PTU treatment, however, the sensitivity to norepinephrine but not to calcium was decreased while the maximal responses to norepinephrine and calcium were reduced together. The attenuated contractile responses to the vasoconstrictors in PTU-treated rats are ascribed to the decreased ability of the muscle cells to contract. On the other hand, the relaxation responses induced by acetylcholine and histamine (endothelium-dependent relaxants) and isoproterenol and sodium nitroprusside (endothelium-independent relaxants) had tendencies to be augmented in aortic rings of PTU-treated rats when compared with those of age-matched control animals. However, the sensitivities to the endothelium-independent relaxants were different between PTU-treated and control rats whereas those to the endothelium-dependent relaxants were not. These results suggest that the altered vascular responsiveness in the PTU-treated rats seems to be due to the alteration of smooth muslce cells rather than the Influence of endothelium, and that this change is slowly progressive after hypothyroidism is evident.

• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.361-371
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• 2003

The vasorelaxant actions and blood pressure lowering of the ${\alpha}_2$-adrenoceptor agonists (${\alpha}_2$-AAs) clonidine and xylazine were investigated in rat isolated aortic rings and anesthesized rats. Both clonidine and xylazine produced a concentration-dependent inhibition of the sustained contraction induced by norepinephrine (NE), but not by KCl. NE-induced contractions were attenuated partly by nifedipine or verapamil, voltage dependent $Ca^{2+}$ channel blockers. These $Ca^{2+}$ channel blockers-resistant contractions were abolished by clonidine or xylazine. Inhibitory effects of a ${\alpha}_2$-AAs on contractions could be reversed by ryanodine, an intracellular $Ca^{2+}$, transport blocker, and tetrabutylammonium (TBA), a $Ca^{2+}$ activated $K^+$ channel blocker, but not by nifedipine, glibenclamide or removal of extracellular $Ca^{2+}$ and endothelium. Moreover, ${\alpha}_2$-AAs produced relaxation in NE-precontracted isolated intact aortic rings in a concentration-dependent manner, but not in KCl-precontracted rings. The relaxant effects of ${\alpha}_2$-AAs were inhibited by ryanodine and TBA, but not by nifedipine, glibenclamide, N (G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), 2-nitro-4-carboxyphenyl N,N-diphenylcarhurnte (NCDC), lithium sulfate, staurosporine or removal of extracellular $Ca^{2+}$ and endothelium. In vivo, infusion of xylazine elicited significant decrease in anerial blood pressure. This xylazinelowered blood pressure was completely inhibited by the intravenous injection of TBA, but not by the intravenous injection of glibenclamide, L-NNA, L-NAME, AG, nifedipine, lithium sulfate or saponin.. These findings showed that the receptor-mediated and ${\alpha}_2$-adrenoceptor A-stimulated endothelium-independent vasorelaxant effect may be explained by decreasing intracellular $Ca^{2+}$ release and activation of $Ca^{2+}$-activated $K^+$ channels, which may contribute to the hypotensive effects of ${\alpha}_2$-AAs in rats.