• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.403-411
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• 1997

To elucidate the mechanism of gentamicin induced renal dysfunction, renal functions and activities of various proximal tubular transport systems were studied in gentamicin-treated rats (Fisher 344). Gentamicin nephrotoxicity was induced by injecting gentamicin sulfate subcutaneously at a dose of 100 $mg/kg{\cdot}day$ for 7 days. The gentamicin injection resulted in a marked polyuria, hyposthenuria, proteinuria, glycosuria, aminoaciduria, phosphaturia, natriuresis, and kaliuresis, characteristics of aminoglycoside nephropathy. Such renal functional changes occurred in the face of reduced GFR, thus tubular transport functions appeared to be impaired. The polyuria and hyposthenuria were partly associated with a mild osmotic diuresis, but mostly attributed to a reduction in free water reabsorption. In renal cortical brush-border membrane vesicles isolated from gentamicin-treated rats, the $Na^+$ gradient dependent transport of glucose, alanine, phosphate and succinate was significantly attenuated with no changes in $Na^+-independent$ transport and the membrane permeability to $Na^+$. These results indicate that gentamicin treatment induces a defect in free water reabsorption in the distal nephron and impairs various $Na^+-cotransport$ systems in the proximal tubular brush-border membranes, leading to polyuria, hyposthenuria, and increased urinary excretion of $Na^+$ and other solutes.

• Journal of Veterinary Clinics
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• v.22 no.4
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• pp.420-423
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• 2005

A 2-year-old 16-kg, intact female lindo was presented with weight loss and poor hair coat. Abnormal serum biochemical values included mild hypokalemia (3.9 mmol/L, reference range 4.37 to 5.35 mmol/L) and mild hyperglycemia (124 mg/dl, reference range 65 to 118 mg/dl). in the complete blood count and diagnostic imaging examination, abnormal changes wer not seen. The analysis of urine sample obtained from cystocentesis revealed glucosuria (> 100 mg/dl) and mild proteinuria. Repeated analysis after admission showed persistent glucosuria and hypokalemia. But blood glucose values did not exceed the renal threshold fur glucose reabsorption. To differentiate cause of the glucosuria, the glucose tolerance test and the low-dosage dexamethasone suppression test were indicated. Results of both tests were normal. In addition, the serum total thyroxine $(T_4)$ value was within normal range. The arterial blood gas analysis showed no remarkable changes. The fractional reabsorption rates of amino acids and phosphorus were calculated above $97\%$. Based on these findings, the dog was diagnosed as renal glucosuria due to proximal renal tubular dysfunction. But this persistent renal glucosuria with hypokalemia may be the initial sign of Fanconi's syndrome or proximal renal tubular acidosis.

• Journal of Acupuncture Research
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• v.19 no.5
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• pp.199-208
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• 2002

Objective : This study was undertaken to determine if Carthami Semen Aquacupunc- ture(CSA) exerts protective effect against alterations in membrane transport function rabbits with mercury chloride(HG)-induced acute renal failure. Methods : The administration of Hg at a subcutaneous single dose of 10 mg/kg caused a reduction in GFR and an increase in fractional Na excretion, indicating generation of acute renal failure. When CSA were given for 7 days prior to Hg administration, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased in rabbits treated with Hg alone. Results : The increase in rabbits treated with Hg following CSA are significantly lower than that in animals treated with Hg alone. Uptakes of glucose and phosphate in purified isolated brush-border membrane and Na-K-ATPase activity in microsomal fraction were inhibited in rabbits treated with Hg alone. Such changes were prevented by CSA. Uptakes of organic ions, PAH and TEA, in renal cortical slices were inhibited by the administration of Hg, which was prevented by CSA. Exposure of renal cortical slices to Hg in vitro caused an increased LDH release and lipid peroxidation, which was significantly prevented by CSA extract. Conclusions : These results indicate that the administration of Hg causes impairment in reabsorption of solutes in the proximal tubule via the generation of reactive oxygen species. CSA provides the protection against the impairment in proximal reabsorption, and its effect may be resulted from its antioxidant effect.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.729-733
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• 1995

This study was carried out to determine the effect of renal ischemia on renal function and excretion of amino acid in rabbit. The animal models of renal ischemia induced experimentally by clamping the renal artery for different lengths of time. These results were summarized as follows: 1. Ischemia for 30 or 60 min produced a polyuria which is accompanied by an increase in $Na^+$ excretion. Glomerular filtration rate (GFR) and p-aminohippurate plasma($C_{PAH}$) were not altered by 30 min of ischemia, indicating that transient ischemia results in a marked tubular dysfuction before a reduction in GFR or renal blood flow. 2. Reabsorption of glucose and amino acids such as alanine and lysine was markedly reduced after 30 min of ischemia, and the effect was more pronounced after 60 min of ischemia.

• Korean Journal of Acupuncture
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• v.23 no.1
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• pp.45-57
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• 2006

Objective : This study was undertaker to determine if Juglandis Semen herbal acupuncture (JSA) exerts protective effect against alterations in membrane transport function in rabbits with mercury-induced acute renal failure. Methods : Nephrotoxicity was induced by subcutaneous administration of Hg(a single dose of 10mg/kg) and JSA was performed at both sides of Shenshu($(BL_{23})$, Sinsu) for 7 days. Results: The administration of Hg at a subcutaneous single dose of 10 mg/kg caused a reduction in GFR to 12% of the basal value and an increase in fractional $Na^+$ excretion to 8.9-fold, indicating generation of acute renal failure. When JSA were given for 7 days prior to Hg administration, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased to approximately 102- and 35-fold, respectively, in rabbits treated with Hg alone. The increase in rabbits treated with Hg following ISA are significantly lower than that in animals treated with Hg alone. Uptakes of glucose and phosphate in purified isolated brush-border membrane and $Na^+-K^+-ATPase$ activity in microsomal fraction were inhibited in rabbits treated with Hg alone, suggesting that impairment in proximal reabsorption of glucose and phosphate is resulted from a direct damage of membrane transport carriers and disruption of the normal $Na^+$ gradient. Such changes were prevented by JSA. Conclusion These results indicate that the administration of Hg causes impairment in reabsorption of solutes in the proximal tubule via the generation of reactive oxygen species. JSA provides the protection against the Hg-induced impairment in proximal reabsorption, and its effect may be resulted from its antioxidant action.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.111-122
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• 2001

Objectives ; This study was undertaken to determine if Salviae Radix herb-acupuncture (SRA) exerts protective effect against alterations in membrane transport function in rabbits with mercury chloride (Hg)-induced acute renal failure. Methods and Results ; The administration of Hg at a subcutaneous single dose of 10mg/kg caused a reduction in GFR to 9.4% of the basal value and an increase in fractional Na+ excretion to 10-fold, indicating generation of acute renal failure. When animals were acupunctured with $0.5m{\ell}$ of SRA extract (0.1%) in both sides of Shinsu(BL23) for 7 days prod to Hg administration, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased to approximately 132-fold and 7-fold, respectively, in rabbits treated with Hg alone, but the fractional excretion of glucose was increased to 26-fold and that of phosphate was not different from the basal value in SRA-pretreated rabbits. Uptakes of glucose and phosphate in purified isolated brush-border membrane and $Na^+-K^+$-ATPase activity in microsomal fraction were inhibited in rabbits treated with Hg alone, suggesting that impairment in proximal reabsorption of glucose and phosphate is resulted from a direct damage of membrane transport carriers and disruption of the normal $Na^+$ gradient. Conclusions ; Such changes were prevented by SRA. Uptakes of organic ions, PAH and TEA, in renal cortical slices were inhibited by the administration of Hg, which was prevented by SRA. Pretreatment of an antioxidant DPPD attenuated the increase in the fractional excretion of glucose and phosphate induced by the administration of Hg.

• Journal of Pharmacopuncture
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• v.10 no.1 s.22
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• pp.23-36
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• 2007

Objective : We performed this study in order to investigate the effects of Paljeongsan-gamibang(八正散加味方) on the renal failure. Methods : We injected 8ml/kg of 50% glycerol on the rats. And then administered Paljeongsan-gamibang extract ; 209mg/200g/day to sample group during 3 days and observed the body temperature, urine volume, stool volume and the levels of creatinine, glucose, inorganic phosphorus, Na+, K+, Cl-, threonine, tyrosine in blood and creatinine, glucose, threonine, tyrosine in urine. Results : 1, The sample group administered Paljeongsan-gamibang showed a suppressive effect of body temperature, an improving effect in capability of concentrating urine at convoluted tubule and showed an increasing effect of stool volume. 2. The sample group administered Paljeongsan-gamibang showed a lowering effect in creatinine level in blood and showed an increasing effect in the levels of inorganic phosphorus, Na+, K+, Cl-, threonine and tyrosine in blood. 3. The sample group administered Paljeongsan-gamibang showed an increasing effect in creatinine level in urine and showed a lowering effect in the levels of glucose, inorganic phosphorus, threonine and tyrosine in urine. Conclusions : Conclusively, Paljeongsan-gamibang was recognized to have a curative effect against the damage of rat kidney induced by 50% glycerol, especially to improve the capability of reabsorption in proximal convoluted tubule.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.189-198
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• 1999

Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.

• The Journal of Korean Diabetes
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• v.19 no.3
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• pp.135-139
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• 2018

The sodium-glucose cotransporter-2 inhibitor (SGLT2i) is a new anti-hyperglycemic agent that have function to concomitantly inhibit the reabsorption of glucose and sodium in the renal proximal convoluting tubule. Recent two cardiovascular outcome trials showed that a lower risk of cardiovascular events with SGLT2i in people with type 2 diabetes. In addition, prior real-world data demonstrated similar SGLT2i effects, but these studies were limited to the United States and Europe. Thus, the CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors) 2 Study was investigated cardiovascular outcomes in those initiated on SGLT2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. In Korea, 336,644 episodes of initiation in SGLT2i or oGLD group between September 2014 and December 2016 were identified in Korea National Health Insurance database after propensity score matching. SGLT2i users was associated with a lower risk of all-cause death (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.67~0.77), hospitalization for heart failure (HHF) (HR, 0.87; 95% CI, 0.82~0.92), all-cause death or HHF (HR, 0.81; 95% CI, 0.78~0.85), myocardial infarction (HR, 0.81; 95% CI, 0.74~0.89), and stroke (HR, 0.82; 95% CI, 0.78~0.86) compared with oGLD users. In conclusion, initiation of SGLT2i had a lower risk of cardiovascular events in people with type 2 diabetes compared with oGLDs.