• Molecules and Cells
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• v.42 no.12
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• pp.893-905
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• 2019

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion processes that closely related to their function. Disruption of mitochondrial dynamics has been demonstrated in acute kidney injury (AKI), which could eventually result in cell injury and death. Previously, we reported that augmenter of liver regeneration (ALR) alleviates renal tubular epithelial cell injury. Here, we gained further insights into whether the renoprotective roles of ALR are associated with mitochondrial dynamics. Changes in mitochondrial dynamics were examined in experimental models of renal ischemia-reperfusion (IR). In a model of hypoxia-reoxygenation (HR) injury in vitro, dynamin-related protein 1 (Drp1) and mitochondrial fission process protein 1 (MTFP1), two key proteins of mitochondrial fission, were downregulated in the Lv-ALR + HR group. ALR overexpression additionally had an impact on phosphorylation of Drp1 Ser637 during AKI. The inner membrane fusion protein, Optic Atrophy 1 (OPA1), was significantly increased whereas levels of outer membrane fusion proteins Mitofusin-1 and -2 (Mfn1, Mfn2) were not affected in the Lv-ALR + HR group, compared with the control group. Furthermore, the mTOR/4E-BP1 signaling pathway was highly activated in the Lv-ALR + HR group. ALR overexpression led to suppression of HR-induced apoptosis. Our collective findings indicate that ALR gene transfection alleviates mitochondrial injury, possibly through inhibiting fission and promoting fusion of the mitochondrial inner membrane, both of which contribute to reduction of HK-2 cell apoptosis. Additionally, fission processes are potentially mediated by promoting tubular cell survival through activating the mTOR/4E-BP1 signaling pathway.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• Applied Microscopy
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• v.34 no.4
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• pp.241-254
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• 2004

Kidney had recovery functions against toxicants, ischemia, reperfusion-induced damage, acute-renal failure (ARF). Urinary epidermal growth factor (EGF) is produced by the juxtaglomerular apparatus. Kidney accumulates or excretes the EGF. In case of renal diseases, excreted EGF was decreased. The aim of this study is to evaluate the effects squalene (SQ) on the prevention of experimental acute renal failure induced by glycerol. In case of in vitro study, we investigated the expression of EGF by RT-PCR. After the proximal tubular cells was isolated, glycerol (1, 2, 4 mM) or glycerol plus squalene (0.1, 0.05 or 0.1%) was added. In case of in vivo study, we investigated the changes of BUN, creatine, and ultrastructure. Experimental groups were divided into four groups. Group 1 was normal mouse. Group 2 was injected with SQ only (180 mg/kg). Group 3 was not treated with squalene after intraperitoneal contamination of glycerol (50%, 8 ml/kg). And, Group 4 was treated with squalene (180 mg/kg) after intraperitoneal contamination of glycerol (50%, 8 ml/kg). All groups were used to 7 mice. In the results, we investigated the glycerol induced renal failure. The expression of EGF mRNA was decreased in renal proximal tubules when treated with only glycerol. SQ increased the mRNA expression of EGF in renal proximal tubules. SQ also quickly recovered the levels of BUN and creatine compared with those of mice treated with only glycerol (P<0.01). In case of ultrastructure, group 3 had heavily damaged mitochondria, but, mitochondria in group 4 had evidences of the recovery. It was concluded that SQ had the recovery effects for the glycerol-induced acute renal failure.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.257-261
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• 2009

Effective therapeutics for renal failures have not yet been developed until now. Recently, there was a report showing that Wen-pi-tang-Hab-Wu-ling-san (WHW) prescriptions had the potential to prevent renal failures through the increased expression of HSP-27 and HSP-72 after ischemia/reperfusion. Therefore, formulation studies by pH-specific released systems were carried out to exhibit the optimal activity of WHW prescriptions in this study. WHW prescriptions were separately extracted using water into two parts of stomach-released (SR) and intestine-released (IR) extracts. Subsequently, the double-layered tablet was prepared using the SR extracts and pharmaceutical additives and enteric-coated IR tablet. Dissolution studies were carried out to figure out the release of cinnamic acid and icarrin from SR tablet, IR tablet and double-layered tablet, respectively. The complete release of cinnamic acid from SR tablet showed 90min after dissolution in pH 1.2 and insignificant drug released from IR tablet. As well as, icarrin from IR tablet completely released in pH 6.8 and 7.4 as enteric-coating film dissolved.

• Journal of Chest Surgery
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• v.45 no.2
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• pp.73-79
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• 2012

Background: Aortic cross clamping is associated with spinal cord ischemia. This study used a rat spinal cord ischemia model to investigate the effect of distal aortic pressure on spinal cord perfusion. Materials and Methods: Male Sprague-Dawley rats (n=12) were divided into three groups. In group A (n=4), the aorta was not occluded. In groups B (n=4) and C (n=4), the aorta was occluded. In group B the distal aortic pressures dropped to around 20 mmHg. In group C, the distal aortic pressure was decreased to near zero. The carotid artery and tail artery were cannulated to monitor the proximal aortic pressure and the distal aortic pressure. Fluorescent microspheres were used to measure the regional blood flow in the spinal cord. Results: After aortic occlusion, blood flow to the cervical spinal cord showed no significant difference among the three groups. In groups B and C, the thoracic and lumbar spinal cord and renal blood flow decreased. No microspheres were detected in the thoracic and lumbar spinal cord of group C. Conclusion: The spinal cord blood flow is dependent on the distal aortic pressure after thoracic aortic occlusion.

• Journal of Chest Surgery
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• v.29 no.4
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• pp.449-453
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• 1996

A successful resection of dissecting thoracoabdominal aortic aneurysm is presented in a patient who had undergone kidney transplantation 20 months previously. Because the transplanted kidney is more sensitive to ischemia than the normal kidney, a femoro-femoral bypass with a pump oxygenator was used for perfusion of the transplanted kidney during crossclamping. During the clamping time of 1)8 minutes, kidney perfusion was maintai ed with a perfusion pressure of (19 to 31) 27mmHg and the flow was 0.53 to 0.81 L/min. 32mm sized Hemashield (22 Cm in length) was interposed. The postoperative course was uncomplicated. We believe that performing the femoro- femoral bypass with a pump oxygenator is an effective and simple method for renal and spinal protection in such operations.

• Journal of Veterinary Clinics
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• v.40 no.6
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• pp.423-428
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• 2023

The mouse kidney transplantation model serves as an invaluable tool for exploring various aspects of the transplant process, including acute rejection, cellular and humoral rejection, ischemia-reperfusion injury, and the evaluation of novel therapeutic strategies. However, conducting venous anastomosis in this model poses a significant challenge due to the thin and pliable characteristics of the renal vein, which often obstruct clear visualization of the resected vein's edge. This study proposes the adoption of a two stay suture technique to enhance the visualization of the renal vein's edge, thereby facilitating efficient and successful venous anastomosis. A total of 22 mice served as kidney donors in this study. The conventional anchoring suture technique was employed for venous anastomosis in 11 of these mice, while the remaining 11 underwent the two stay suture technique. The anastomosis duration and completion rates were then compared between these two groups. The conventional anchoring suture technique yielded an average anastomosis time of 29 minutes and a completion rate of 64%. In contrast, the two stay suture technique demonstrated a substantial improvement, with an average anastomosis time of 14 minutes and a completion rate of 100%. The two stay suture technique offers a promising solution to enhance visualization during venous anastomosis in murine kidney transplantation. This technique may particularly benefit novices by enabling them to perform venous anastomosis more easily, swiftly, and successfully.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.333-340
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• 2016

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i .p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a significant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i .p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.

• Herbal Formula Science
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• v.31 no.3
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

• Journal of Chest Surgery
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• v.35 no.4
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• pp.255-260
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• 2002

Paraplegia remains unresolved as the most dreaded operative complication with surgical treatment of descending thoracic and thoracoabdominal aortic diseases. In this study, the neuroprotective effect of trimetazidine that has been used clinically for ischemic heart disease was investigated in a rabbit spinal cord ischemia model. Material and Method: Thirty-three New Zealand white rabbits were randomized as follows: control group undergoing abdominal aortic occlusion but receiving no pharmacologic intervention(Group 1, n= 17); TMZ group(Group 2, n= 16) receiving 3 mg/kg trimetazidine intravenously before the occlusion of the aorta. Ischemia was induced by clamping the abdominal aorta just distal to the left renal artery for 30 minutes. Neurologic status was assessed at 2, 24, and 48 hours after the operation according to the modified Tarlov scale, then the lumbosacral spinal cord was processed for histopathologic examinations 48 hours after the final assessment. Result: The average motor function score was significantly higher in the TMZ group(3.20 $\pm$ 0.77 vs 1.13 $\pm$ 1.25 at 2 hours, 3.50 $\pm$ 0.76 vs 1.45 $\pm$ 1.57 at 24 hours, and 3.91 $\pm$ 0.30 vs 1.86 $\pm$ 1.86 at 48 hours after operation; p value$\leq$0.05). Histologic observations were correlated with the motor scores. Conclusion: The results suggested that trimetazidine reduced spinal cord injury during aortic clamping and that it may have clinical utility for the thoracoabdominal aortic surgery: