• Advances in Traditional Medicine
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• v.9 no.4
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• pp.292-302
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• 2009

Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. Previous studies showed that antioxidant treatments attenuated renal ischemia/reperfusion injury. The objective of this study was to examine the role of hesperidin in modulating reactive oxygen species induced inflammation and apoptosis after renal ischemia/reperfusion injury. Rats were subjected to right nephrectomy, 15 days later 45 min of renal ischemia and 24 h reperfusion with or without treatment with hesperidin. Renal function, inflammation and apoptosis were compared at 24 h after reperfusion injury. Hesperidin improved the renal dysfunction and reduced inflammation and apoptosis after ischemia/reperfusion injury. In conclusion, hesperidin shows potent anti-apoptotic and antiinflammatory properties due to antioxidant property. These findings may have major implications in the treatment of human ischemic acute renal failure.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.7-15
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• 2013

Objectives : Interruption and subsequent restoration of blood flow into the kidney result in renal injury. As an approach to preventing the renal injury, we determined the optimal conditions and the underlying mechanisms by which supernatant of hot water extract of ground Triticum aestivum L. (extract) attenuated ischemia/reperfusion (I/R) injury. Methods : One hour after administration of the extract (400 mg/kg) by intraperitoneal injection, renal I/R injury was generated by clamping the left renal artery in rats after surgical removal of the right kidney, followed by reperfusion. The maximal difference between the vehicle-treated and the extract-treated group under ketamine/xylazine or enflurane anesthetization was assessed at varying periods of ischemia (30-45 min) and reperfusion (3-48 hr), based on the renal function assessed with serum creatinine levels, tissue injury with hematoxylin/eosin staining, and apoptosis with terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining. Results : Enflurane anesthetization with 40 min of ischemia and 24 hr of reperfusion was identified to be the optimal condition, under which condition serum creatinine levels and tubular damage in the extract-treated group were significantly reduced compared with those in the vehicle-treated group ($1.3{\pm}0.2$ versus $2.7{\pm}0.3$ mg/dL, P < 0.01, and average score $1.8{\pm}0.1$ versus $3.5{\pm}0.3$, P < 0.01, respectively). These beneficial effects were mediated by inhibition of apoptotic cascades through attenuation of renal tissue malondialdehyde levels, Bax/Bcl-2 ratio and caspase-3 levels. Conclusions : The extract conferred renal protection against ischemia/reperfusion injury in rats by scavenging reactive oxygen species and consequently blocking apoptotic cascades, plausibly augmented by enflurane protection.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.135-143
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• 2013

Objectives : The purpose of this study was to determine whether the methanol extract of Cassia mimosoides var. nomame Makino, a naturally growing plant in Korea, could prevent the renal-ischemia/reperfusion injury in a rat model or not. Methods : The radical scavenging activities of the extracts, and ascorbic acid as a positive control, were measured in vitro. At one hour after an intraperitoneal injection of the extract (400 mg/kg), renal ischemia/reperfusion injury was generated by 40 min clamping of the left renal artery in rats. After renal ischemia/reperfusion and 24 hr restoration of blood circulation, the serum creatinine concentration was measured. And the extent of epithelial cell injury and apoptosis was assessed by various staining technologies. The Bax/Bcl-2 ratio and activated caspase-3 were assessed by immunohistochemistry. Results : The extract showed a slightly lower level of radical scavenging activity than that of ascorbic acid. Compared to those of the vehicle-treated group, the extract-treated group displayed a significantly smaller tubular epithelial cell injury of 54% reduction in the outer medulla region and a lower serum creatinine concentration of 50% reduction. It seems that the reduction in cellular injury is due to the attenuation of the Bax/Bcl-2 ratio, and the inhibition of caspase-3 activation by the extract of Cassia mimosoides. Conclusions : Cassia mimosoides var. nomame Makino could be a good candidate for a prophylactic agent against the ischemia/reperfusion/induced kidney injury.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2006.11a
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• pp.105-105
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• 2006

• Journal of Ginseng Research
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• v.40 no.2
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• pp.196-202
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• 2016

Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

• 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.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.98-102
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• 2006

The present stuby was carried out to determine if Radix Glycyrrhizae extract exerts beneficial effect against the ischemia-induced acute renal failure in rabbits. Radix Glycyrrhizae was known to reinforce the function of the spleen and replenish Qi, remove heat and counteract toxicity, dispel phlegm and relieve cough, alleviate spasmodic pain, and to moderate drug actions. It's indications are weakness of the spleen and the stomach marked by lassitude and weakness; cardiac palpitation and shortness of breath; cough with much phlegm; spasmodic pain in the epigastrium, abdomen and limbs; carbuncles and sores. It is often used for reducing the toxic or drastic actions of other drugs. Rabbits were treated with Radix Glycyrrhizae extract via i.v., followed by renal ischemia/reperfusion. Fractional excretion of glucose and phosphate, lipid peroxidation and light microscopy were done to evaluate the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced acute renal failure. Renal ischemia/reperfusion caused increase of fractional excretion of glucose and phosphate increased in ischemia-induced animals, which was partially prevented by Radix Glycyrrhizae extract treatment. Ischemia/reperfusion increased lipid peroxidation, which was prevented by Radix Glycyrrhizae extract administration. And the beneficial effect of Radix Glycyrrhizae extract on ischemia/reperfusion induced kidney injury was shown through the light micrographic observation. These results indicate that lipid peroxidation plays a critical role in ischemia-induced acute renal failure. Radix Glycyrrhizae extract exerts the protective effect against acute renal failure induced by renal ischemia/reperfusion.

• Preventive Nutrition and Food Science
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• v.17 no.2
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• pp.101-108
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• 2012

Interruption or prolonged reduction and subsequent restoration of blood flow into the kidney triggers the generation of a burst of reactive oxygen species (ROS), leading to injury in the tubular epithelial cells. In this study, we determined whether methanol extract of goat's-beard (Aruncus dioicus) (extract) could prevent this ischemia/reperfusion injury. When in vitro radical scavenging activity of the extract was measured using a DPPH radical quenching assay, the extract displayed slightly lower activity than ascorbic acid. One hour after administration of the extract (400 mg/kg) by intraperitoneal injection in rats, renal ischemia/reperfusion injury was generated by clamping the left renal artery for forty minutes, followed by 24 hr restoration of blood circulation. Prior to clamping the left renal artery, the right renal artery was removed. Compared with the vehicle-treated group, pretreatment with the extract significantly reduced the tubular epithelial cell injury by 37% in the outer medulla region, and consequently reduced serum creatinine concentration by 39%. Reduction in the cell injury was mediated by attenuation of Bax/Bcl-2 ratio, inhibition of caspase-3 activation from procaspase-3, and subsequent reduction in the number of apoptotic cells. Thus, goat's-beard (Aruncus dioicus) might be developed as a prophylactic agent to prevent acute kidney injury.

• Journal of Veterinary Clinics
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• v.19 no.3
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• pp.299-302
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• 2002

Selectins are differentially expressed carbohydrate binding proteins involved in the initiation of tissue inflammation by mediating the rolling and tethering of leukocytes on the vascular endothelium. This primary event in initiation of inflammation, as occurs during reperfusion injury, can be therapeutically targeted using selectin inhibitors, which generally block binding of sLex to E-, P-, and L-selectins. The objective of this study was to determine the role of selectins in renal ischemia/reperfusion injury after kidney transplantation. Canine kidneys were subjected to 60-min warm ischemia, flushed with UW solution, cold stored for 24 h, and autotransplanted into the nephrectomized donor. Renal autografts were monitored for 7 days by serum creatinine in the first study and by histology and myeloperoxidase activity after 4-hour reperfusion in the second study. In each study, one group of animals received TBC1269 (selectin inhibitor) and the other received saline vehicle. Serum creatinine rose quickly after transplantation and was not different between the groups. TBC1269 abolished a reperfusion-induced 2-fold increase in renal cortex neutrophil infiltration and improved histologic signs of ischemia after 4 hours of reperfusion. Selectin blockade does not improve the course of injury caused by warm renal ischemia. A minor benefit associated with the inhibition of early inflammation during reperfusion after kidney transplantation seems to occur.