• YAKHAK HOEJI
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• v.44 no.6
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• pp.558-565
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• 2000

SK-1080 is one of the newly developed orally active nonpeptide angiotensinII $AT_1-receptor$ antagonist that selectively acts at $AT_1$ receptor with high affinity. The cardiac effect on ischemia/reperfusion injury of SK-1080 was compared with those of losartan, a prototype of this class, in isolated rat hearts. Isolated perfused rat heart was pretreated with drug for 10 min and then subjected to global ischemia for 30 min followed by reperfusion with- or without drug for 30 min. The possible additive effect of SK-1080 on the platelet aggregation and coagulation in human blood was also studied. We investigated whether SK-1080 effects the platelet aggregation induced by ADP, a platelet agonist partially dependent on $thromboxaneA_2$. The clotting times in the prothrombin time (PT) and activated partial thromboplastin time (APTT) were also examined in human plasma in vitro as coagulation screening test. SK-1080 improved reperfusion function (LVDP, left ventricular developed pressure; PRP, rate-pressure product) in a dose-dependent manner. SK-1080 reduced ADP-induced platelet aggregation compared with vehicle but less than losartan, and did not affect clotting times.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.225-231
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• 2004

This study was designed to investigate the effect of Trolox, a hydrophilic analogue of vitamin E, on the alteration of vasoregulatory gene expression during hepatic ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia in vivo. The rats were treated intravenously with Trolox (2.5 mg/kg) or the vehicle as a control 5 min before reperfusion. Liver samples were obtained 5 h after reperfusion for a RT-PCR analysis on the mRNA for the genes of interest. These mRNA peptides are endothelin-1 (ET -1), potent vasoconstrictor peptide, its receptor $ET_A$ and $ET_B$, vasodilator endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), heme oxygenase-1 (HO-1), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and cyclooxygenase-2 (COX-2). It was seen that serum alanine aminotransferase and lipid peroxi-dation levels were markedly increased after I/R and Trolox significantly suppressed this increase. In contrast, the glutathione concentration decreased in the I/R group, and this decrease was inhibited by Trolox. ET-1 mRNA expression was increased by I/R, an increase which was prevented by Trolox. The mRNA levels for $ET_A$ receptor was significantly decreased, whereas ET$_{B}$ receptor transcript increased in the I/R group. The increase in $ET_A$ was prevented by Trolox. The mRNA levels for iNOS and HO-1 significantly increased in the I/R group and Trolox attenuated this increase. There were no significant differences in eNOS mRNA expression among any of the experimental groups. The mRNA levels for COX-2 and TNF-$\alpha$ significantly increased in I/R group and Trolox also attenuated this increase. Our findings suggest that I/R induces an imbalanced hepatic vasoregulatory gene expression and Trolox ameliorates this change through its free radical scavenging activity.y.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.7-12
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• 1990

Cyclobuxine D is a steroidal alkaloid, which was extracted from Buxus microphylla var. koreana Nakai. In our previous studies, we clarified several pharmacological actions of cyclobuxine D: an antiinflammatory action, hypotensive and bradycardiac effects, negative inotropic effects on the several smooth muscles and cardiac muscle. The present study was undertaken to elucidate possible mechanisms by protection of myocardial tells from ischemia and reperfusion induced derangement in cardiac function and metabolism by cyclobuxine D. For this purpose, the isolated rat heart was used. Rat hearts were perfused for 60 min under ischemia conditions in the presence and absence of cyclobuxine D and verapamil, and for 30 min under reperfusion conditions. Ischemia produced a marked decline in contractile force, an increase of resting tension, an immediate release of ATP metabolites and an accumulation of calcium in the left ventricle. Cyclobuxine D (100ng/ml) ameliorated the myocardial injury produced by ischemia.

• Journal of Veterinary Clinics
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• v.25 no.3
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• pp.165-169
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• 2008

Renal ischemia-reperfusion (I/R) injury is great clinical important because viability of the organ depends on the tolerance to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of premedicated ascorbic acid alone in I/R injury model induced by cross-clamping of renal vessels. In the rabbit models, 2-4 kg New Zealand white rabbits were subjected to 30 minutes of warm unilateral renal ischemia followed by removal of contralateral kidney and then divided into five groups, control (2) arid treatment groups (3). In control group 1, the rabbits only received right nephrectomy. In control group 2, the rabbits received I/R on left kidney after the right nephrectomy. In treatment group 1, the rabbits received ascorbic acid 50 mg/kg IV before the operation. In treatment group 2, the rabbits received ascorbic acid 100 mg/kg IV before the operation. In treatment group 3, the rabbits received ascorbic acid 200 mg/kg IV before the operation. Blood samples were collected from these rabbits for measurement of kidney function tests at the 0, 1 st, 3rd and 7th day and antioxidant enzyme( SOD, GSHPx, CAT) at 24 hours. Kidney function tests (serum creatinine and BUN) showed a significant difference between group 2 and group 4, 5. Activity of antioxidant enzymes in plasma were significant decrease in group 4, 5 compare to group 2. The result of this study suggested that the exogenous ascorbic acid had a role of attenuation of renal I/R injury in rabbit model.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.169-173
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• 2013

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT ($500{\mu}g/kg$) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.85-85
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• 2001

Sam-Hwang-Sa-Shim-Tang(SHSST), a traditional Chinese medicine, composed of Rhei rhizoma, Scutellaria radix, and Coptidis rhizoma were used in the several disease including hypertension, constipation, and hemorrhage. In the present study, we investigated the neuroprotective effects of SHSST and its ingredients on the ischemia/ reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min and reperfusion was continued for 22 h. SHSST (450 mg/kg), Rhei rhii oma (100 mg/kg), Coptidis rhizoma (100 mg/kg), and Scutellaria radik (100 mg/kg) were orally administered twice, promptly prior to reperfusion and 2 h after the repefusion. Total infarction volume in the ipsilateral hemisphere of ischemia/ reperfusion rats was significantly lowed by the treatments of SHSST (39.2%) and Scutellaria radix (66.5%). However, Coptidis rhizoma did not show any significant effects on the total infarct volume. The inhibiting effect of Scutellaria radix on the total infarct volume was more potent than that of SHSST. In addition, Scutellaria radix significantly inhibited myeloperoxidase (MPO) activity, an index of neutrophil infiltration in ischemic brain tissue. However, there was marked mismatch between total infarct volume and MPO activity in the Scutellaria radix-treated rats. Our findings suggest that Scutellaria radix as an ingredient of SHSST plays a protective role in ischemia-induced brain injury by inhibiting neutrophil infiltration. The effects of Rhei rhizoma on transient brain ischemia-induced neuronal injury are under study.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.335-338
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• 2003

It is thought that highly reactive oxygen species generated after strokes plays a key role in damaging the brain. We examined free radical scavenging activity and neuroprotective effects of several medicinal herbs in a rat model of transient ischemia. Free radical scavenging property of medicinal herbs was examined in vitro using 1,1-diphenyl-2-picrylhydrazyl stable free radical. Transient ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min, followed by reperfusion for 22 hr in rats. Aqueous extracts of 8 medicinal herbs (200 mg/kg) were orally administered twice to transient ischemic rat prior to reperfusion and 2 hr after reperfusion. Total infarction volume in the hemisphere ipsilateral to the ischemia-reperfusion was significantly decreased in 7 groups treated with Sophora flavescens, Lycopus lucidus, Sanguisorba officinalis, Caesalpinia sappan, Albizia julibrissin, Rubia akane, Psoralea corylifolia, or Prunella vulgaris. However, neuroprotective effects of these medicinal herbs were not correlated with their antioxidative activities. These results suggest that these medicinal herbs exert neuroprotection via antioxidative as well as unknown mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• Archives of Reconstructive Microsurgery
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• v.14 no.2
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• pp.85-94
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• 2005

Purpose: This study was to evaluate the effect of ${\alpha}-lipoic$ acid, a potent free radical scavenger, on the expression of active form of extracellular signal-regulated kinase (pERK1/2) proteins from hindlimb muscles of rats following ischemia-reperfusion injury. Material and methods: 64 health, $280{\sim}350\;g$ weighted Sprague-Dawley male rats were used. In order to make a muscle flap, the gastrocnemius (GC) and soleus (SOL) muscles were dissected and elevated. The popliteal artery was occluded for 4hours and reperfused for 10 minutes, 30 minutes, 1 hour, 2 hours and 4 hours, respectively. Results: The ischemia by occlusion of the popliteal artery itself caused a minimal change in expression of phosphorylated form of proteins observed in hindlimb muscle. In contrast, after 4 hours of ischemia, immunoreactivity for pERK1/2 in the GC muscle showed dual peaks at 10 minutes and 4 hours after reperfusion. In ${\alpha}-lipoic$ acid treated group, the expression of pERK1/2 was increased significantly compared to I/R-only group. Conclusion: These results suggest that ${\alpha}-lipoic$ acid may protect I/R injury of the skeletal muscle through free radical scavening and activation of intracellular pERK1/2 expression.

• Journal of Veterinary Clinics
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• v.25 no.4
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• pp.257-262
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• 2008

Renal ischemia-reperfusion injury is great clinical important because viability of the transplanted organ depends on the tolerance of the graft to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of irrigation-aspiration in ischemia-reperfusion injury model induced by cross-clamping of renal vessels. Blood samples were collected from these dogs for measurement of kidney function and antioxidant enzyme activity, and RI at the intrarenal artery was measured at different time intervals. And the kidneys were taken for histopathologic evaluation at day 14. Kidney function (Cr and BUN) showed a significant increasing in untreated group compared to treated group. Resistive index of intrarenal artery was no significant difference among the groups. Activity of antioxidant enzymes in plasma was significant decrease in untreated group compare to control group while in treated group was no significant difference compared to control group. In histopathologic finding, treated group was showed less damage than that of untreated group. This result suggests that the processing of irrigation-aspiration is useful to reducing ischemia-reperfusion injury.