• The Korean Journal of Physiology
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• 제25권2호
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• pp.171-177
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• 1991

This study was carried out to determine effect of acute renal ischemia on transport function of organic cation, tetraethylammonium (TEA), in rabbit kidney proximal tubule. Clamping of the renal artery for 30 and 60 min produced a polyuria which was accompanied by an increase in $Na^+$ excretion. The capacity of kidney cortical slices to accumulate TEA was increased after 30 and 60 min of ischemia. When blood flow was restored for 30 min after 30 and 60 min of ischemia, the augmented TEA uptake was recovered to the control values. Oxygen consumption of cortical slices was stimulated after 30 min of ischemia, whereas it was not altered by 60 min of ischemia. A 90-min ischemia produced a significant inhibition of TEA uptake and tissue oxygen consumption. These results suggest that the basolateral transport system for organic cation persists after ischemic periods of 60 min despite evidence that tubular reabsorptive mechanism of $Na^+$ and water is markedly impaired. This may indicate that the active secretory systems of proximal tubule are more resistant to ischemic injury than the reabsorptive systems.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2006년도 추계학술대회 및 정기총회
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• pp.105-105
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• 2006

• 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.

• 대한한의학방제학회지
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• 제29권1호
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• pp.33-44
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• 2021

Renal ischemia-reperfusion injury(IRI), an important cause of acute renal failure (ARF), cause increased renal tubular injury. Jesaeng-sinkihwan (JSH) was recorded in a traditional Chines medical book named "Bangyakhappyeon (方藥合編)". JSH has been used for treatment of diabetes and glomerulonephritis with patients. Here we investigate the effects of Jesaeng-sinkihwan (JSH) in a mouse model of ischemic acute kidney injury. The animals model were divided into four groups at the age of 8 weeks; sham group: C57BL6 male mice (n=9), I/R group: C57BL6 male mice with I/R surgery (n=9), JSH Low group: C57BL6 male mice with surgery + JSH 100 mg/kg/day (n=9) and JSH High group: C57BL6 male mice with surgery + JSH 300 mg/kg/day (n=9). Ischemia was induced by clamping the both renal arteries during 25 min, and reperfusion was followed. Mouse were orally given with JSH (100 and 300 mg/kg/day during 3 days after surgery. Treatment with JSH significantly ameliorates creatinine clearance(Ccr), Creatinine (Cr) and blood urea nitrogen(BUN) in obtained plasma. . Treatment with JSH reduced kidney inflammation markers such as Neutrophil Gelatinase Associated Lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). JSH also reduced the periodic acid schiff (PAS) staining intensity and picro sirius red staining intensity in kidney of I/R group. These findings suggest that JSH ameliorates tubular injury including renal dysfunction in I/R induced ARF mouse.

• 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.

• BMB Reports
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• 제43권9호
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• pp.629-634
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• 2010

Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS.

• 한국임상수의학회지
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• 제19권3호
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• pp.299-302
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• 2002

Selectin은 조직 염증반응의 초기화에 관여하는 결합 단백질이며, 맥관내피에서 백혈구의 rolling과 tethering을 매개한다. 따라서 selectin inhibitor를 이용하여, 이들 selectin의 수용체인 sLex 에 대한 block을 유도함으로서 염증반응의 초기화를 억제할 수 있다는 가정하에, 본 연구에서는 장기이식 후 reperfusion에서 발생하는 손상에 대한 selectin inhibitor의 효과를 알아보았다. Beagle 견을 사용하여 신장이식을 실시하였다 공여 신장은 60분의 warm ischemia를 유도한 후 UW solution으로 관류하고 24시간동안 냉장보관하여 자가이식하였으며, 반대쪽 신장은 적출하였다. 술 후 7일동안 혈청 creatinine치를 측정하였다 2차실험으로, 12마리의 Beagle견을 사용하여 4시간의 reperfusion 후 조직학적 변화와 myeloperoxidase의 활성을 조사하였다. 각 실험의 대조군은 생리 식염수를,비교군은 TBC1269 (selectin inhibitor)를 신장 적출 전과 신장이식 수술 후 reperfusion 직전에 각각 투여하였다. 혈청 creatinine은 신장이식후 급격히 증가 하였으나, 두군 사이에 유의적인 차이는 없었다. 신장피질의 백혈구 침윤은, 4시간 reperfusion후 생리식염수를 투여받은 군에서 2배의 유의적인 증가를 보였다. 그러나, TBC 1269로 처리한 군에서는 백혈구의 침윤이 유의적인 억제를 보였으며, 허혈에의한 조직학적 변화도 유의적으로 적었다. 개의 신장이식 수술에서 Selectin의 차단은 warm renal ischemia에서 기인된 손상을 개선하지는 못하나, 백혈구의 침윤을 억제하므로 delayed graft function과 관련된 술 후 염증반응의 초기화를 억제하는 효과가 있는 것으로 사료된다.

• 한국임상수의학회지
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• 제26권3호
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• pp.200-204
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• 2009

This study was performed to evaluate the effects of reduced L-glutathione on the oxidant/antioxidant status(superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GPx), protein carbonyl and lipid hydroperoxide(LPO) concentration), renal function(blood urea nitrogen(BUN) and serum creatinine levels), and microscopy of renal tissues in pigs undergoing unilateral renal ischemia-reperfusion(I/R). Sixteen Landrace and Yorkshire mixed-breed pigs were divided randomly into two groups: untreated control group and reduced L-glutathione-treated group(4 mg/kg IV). Each group had 8 pigs. Pigs were unilaterally nephrectomized and the kidney was subject to 30 min of renal pedicle occlusion. Blood samples for biochemical assay were collected on days 1, 3, 5, 7, and 14 post nephrectomy. Renal I/R injury were evaluated histopathologically by the microscopic observation of renal tissue sections and biochemically by the measurement of the plasma creatinine and urea levels. Parameters of oxidative stress such as SOD, GPx, CAT, protein carbonyl and LPO were measured. The elevation of creatine and BUN levels was lower in the treated group, compared with the control group. The activities of antioxidant-enzyme were higher in the treated group, compared with the control group. In histological findings, the severity of damage in the reduced L-glutathione treated group was less when compared to the control group.

• 대한의생명과학회지
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• 제11권4호
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• pp.441-446
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• 2005

The molecular mechanism of ischemia/reperfusion injury remains unclear. Reactive oxygen species (ROS) are implicated in cell death caused by ischemia/reperfusion in vivo or hypoxia in vitro. Poly (ADP-ribose) polymerase (PARP) activation has been reported to be involved in hydrogen peroxide-induced cell death in renal epithelial cells. This study was therefore undertaken to evaluate the role of P ARP activation in chemical hypoxia in opossum kidney (OK) cells. Chemical hypoxia was induced by incubating cells with antimycin A, an inhibitor of mitochondrial electron transport. Exposure of OK cells to chemical hypoxia resulted in a time-dependent cell death. In OK cells subjected to chemical hypoxia, the generation of ROS was increased, and this increase was prevented by the $H_2O_2$ scavenger catalase. Chemical hypoxia increased P ARP activity and chemical hypoxia-induced cell death was prevented by the inhibitor of PARP activation 3-aminobenzamide. Catalase prevented OK cell death induced by chemical hypoxia. $H_2O_2$ caused PARP activation and $H_2O_2-induced$ cell death was prevented by 3-aminobenzamide. Taken together, these results indicate that chemical hypoxia-induced cell injury is mediated by PARP activation through H202 generation in renal epithelial cells.

• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.661-670
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• 2018

Fimasartan, a new angiotensin II receptor antagonist, reduces myocyte damage and stabilizes atherosclerotic plaque through its anti-inflammatory effect in animal studies. We investigated the protective effects of pretreatment with fimasartan on ischemia-reperfusion injury (IRI) in a mouse model of ischemic renal damage. C57BL/6 mice were pretreated with or without 5 (IR-F5) or 10 (IR-F10) mg/kg/day fimasartan for 3 days. Renal ischemia was induced by clamping bilateral renal vascular pedicles for 30 min. Histology, pro-inflammatory cytokines, and apoptosis assays were evaluated 24 h after IRI. Compared to the untreated group, blood urea nitrogen and serum creatinine levels were significantly lower in the IR-F10 group. IR-F10 kidneys showed less tubular necrosis and interstitial fibrosis than untreated kidneys. The expression of F4/80, a macrophage infiltration marker, and tumor necrosis factor $(TNF)-{\alpha}$, decreased in the IR-F10 group. High-dose fimasartan treatment attenuated the upregulation of $TNF-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 in ischemic kidneys. Fewer TUNEL positive cells were observed in IR-F10 compared to control mice. Fimasartan caused a significant decrease in caspase-3 activity and the level of Bax, and increased the Bcl-2 level. Fimasartan preserved renal function and tubular architecture from IRI in a mouse ischemic renal injury model. Fimasartan also attenuated upregulation of inflammatory cytokines and decreased apoptosis of renal tubular cells. Our results suggest that fimasartan inhibited the process of tubular injury by preventing apoptosis induced by the inflammatory pathway.