• Journal of Ginseng Research
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• 제40권2호
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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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• 제17권2호
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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.

• 대한본초학회지
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• 제28권6호
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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.

• 한국임상수의학회지
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• 제28권1호
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• 한국임상수의학회지
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• 제25권3호
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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.

• 대한한방내과학회지
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• 제20권1호
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• pp.111-121
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• 1999

Cervus elaphus (CE), being known to reinforce Kidney, have tested to study the effects concerning damages of renal tissue induced by oxygen free radicals. I had observed the effects of CE extract on damages of rat's kidney following ischemia and reflow. Before ischemia was caused, CE extract was applied $0.2m{\ell}$ per 250g through femoral vein in ischemia and reflow group and normal sailine was applied in normal group, Ischemia was caused by renal artery's clamp for 60 min and reflowed by clamp remove after 30 min. It was increased on the content of lipid peroxidation, activies and type conversion ratio of xanthine oxidase following ischemia and reflow. by clamp remove after 30 min. It was increased on the content of lipid peroxidation, activies and type conversion ratio of xanthine oxidase following ischemia and reflow. However, they were decreased when CE extract was pre-applied. Glutathione level was decreased in ischemia and reflow group, and increased in CE extract's pre-applied group. However, it could not seen special changes on aldehyde oxidase activities, either. In conclusion, CE extract recovers the damage of kidney due to ischemia and reflow by decreasing the lipid peroxidation.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.413-423
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• 2021

Apoptosis is proved responsible for renal damage during ischemia/reperfusion. The regulation for renal apoptosis induced by ischemia/reperfusion injury (IRI) has still been unclearly characterized to date. In the present study, we investigated the regulation of histone acetylation on IRI-induced renal apoptosis and the molecular mechanisms in rats with the application of curcumin possessing a variety of biological activities involving inhibition of apoptosis. Sprague-Dawley rats were randomized into four experimental groups (SHAM, IRI, curcumin, SP600125). Results showed that curcumin significantly decreased renal apoptosis and caspase-3/-9 expression and enhanced renal function in IRI rats. Treatment with curcumin in IRI rats also led to the decrease in expression of p300/cyclic AMP response element-binding protein (CBP) and activity of histone acetyltransferases (HATs). Reduced histone H3 lysine 9 (H3K9) acetylation was found near the promoter region of caspase-3/-9 after curcumin treatment. In a similar way, SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), also attenuated renal apoptosis and enhanced renal function in IRI rats. In addition, SP600125 suppressed the binding level of p300/CBP and H3K9 acetylation near the promoter region of caspase-3/-9, and curcumin could inhibit JNK phosphorylation like SP600125. These results indicate that curcumin could attenuate renal IRI via JNK/p300/CBP-mediated anti-apoptosis signaling.

• International Journal of Stem Cells
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• 제16권2호
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• pp.168-179
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• 2023

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods and Results: Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions: The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

• 생명과학회지
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• 제20권4호
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• pp.555-560
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• 2010

이 연구는 Hsp70.1 유전자가 결핍된 생쥐를 이용하여 운동전처치에 따른 신장허혈재관류손상에서 혈청 크레아틴, 신장에서 CuSOD와 MnSOD의 발현변화를 관찰하는데 그 목적을 두고 있다. 실험동물은 c57/BL6 계 수컷(wild type: WT)과 Hsp70.1 knockout (KO) 생쥐를 정상대조군(n=8), 운동군(n=8), 허혈운동군(n=8) 및 허혈군(n=8)의 4군으로 분류하여 이용하였다. 실험종료 후 마취를 한 후 혈청 creatinine을 분석하기 위해서 신장에서 혈액을 추출하였고, 신장을 적출하여 western blot 으로 eCuSOD와 MnSOD 발현변화를 비교하였다. KO 허혈군에서의 CuSOD, MnSOD는 다른 군에 비해 유의하게 낮게(p<0.001, p<0.05) 발현하였으며, creatinine은 높은(p<0.001)농도로 나타났다. 반면 WT에서는 유의한 변화가 나타나지 않았다. 흥미롭게도 KO허혈운동군에서의 CuSOD, MnSOD는 허혈군보다 뚜렷하게 증가하였으며, creatinine은 허혈군에 비해 현저히 감소(p<0.01)하였다. 이상의 결과를 종합하면 Hsp70은 신장허혈재관류손상에 직접적인 관련이 있음을 추정할 수 있다. 따라서 운동전 처치는 허혈성신장기능저하에 예방할 수 있다고 생각된다.

• Preventive Nutrition and Food Science
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• 제17권2호
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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.