• Journal of Acupuncture Research
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• v.17 no.3
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• pp.208-218
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• 2000

This study was undertaken to determine if Salviae Radix (SR) exerts protective effect against oxidant-induced inhibition of phosphate uptake in renal proximal tubular cells. Membrane transport function and cell death were evaluated by measuring phosphate uptake and trypan blue exclusion, respectively, in opossum kidney (OK) cells, an established proximal tubular cell line. $H_2O_2$ was used as a model oxidant. $H_2O_2$ inhibited the phosphate uptake in a dose-dependent manner over the concentration range of 0.1-0.5 mM. Similar fashion was observed in cell death. However, the phosphate uptake was more vulnerable to $H_2O_2$ than cell death, suggesting that $H_2O_2$-induced inhibition of phosphate uptake is not totally attributed to cell death. Decreasedphosphate uptake was associated with ATP depletion and inhibition of $Na^+$-pump activity as determined by direct inhibition of $N^+-K^+$-ATPase activity. When cells were treated with $H_2O_2$ in the presence of 0.05% SR, the inhibition of phosphate uptake and cell death induced by $H_2O_2$ was significantly attenuated. SR restored ATP depletion and decreased $Na^+-K^+$-ATPase activity, and this is likely responsible for the protective effect of SR on decreased phosphate uptake. The protective effect of SR was similar to the $H_2O_2$ scavenger catalase. SR reacts directly with $H_2O_2$ to reduce the effective concentration of the oxidant. The iron chelator deferoxamine prevented the inhibition of phosphate uptake and cell death induced by $H_2O_2$, suggesting that $H_2O_2$-induced cell injury is resulted from an iron-dependent mechanism. These results indicate that SR exerts the protective effect against $H_2O_2$-induced inhibition of phosphate uptake by reacting directly with $H_2O_2$ like the $H_2O_2$scavenger enzyme catalase, in OK cells. However, the underlying mechanism remains to be explored.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.425-434
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• 1997

Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the $Na^+$ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II $(>10^{-9}\;M)$ inhibited $Na^+$ uptake and increased $[Ca^{2+}]_i\;level$ in the PTCs. However, low concentrations of $(<10^{-11}\;ANG\;II)$ stimulated $Na^+$ uptake and did not affect $[Ca^{2+}]_i\;level$. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis$({/beta}-amino\;ethyl ether)-N,N,N'$, N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on $Na^+$ uptake. When ANG II and bradykinin (BK) were treated together, $Na^+$ uptake was further reduced $(88.47{\pm}1.98%\;of\;that\;of\;ANG\;II,\;81.85{\pm}1.84%\;of\;that\;of\;BK)$. In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of $Na^+$ uptake. Arachidonic acid reduced $Na^+$ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on $Na^+$ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine $(10^{-6}\;M)$ and AACOCF3 $(10^{-5}\;M)$ for 1 hr before the addition of $(<10^{-9}\;ANG\;II)$, the inhibitory effect of ANG II was reversed. In addition, econazole $(>10^{-6}\;M)$ blocked ANG II-induced inhibition of $Na^+$ uptake. In conclusion, the $[Ca^{2+}]_i$ (calcium-calmodulin-dependent kinase) and phospholipase $A_2\;(PLA_2)$ metabolites are involved in the inhibitory effects of ANG II on $Na^+$ uptake in the PTCs.

• Childhood Kidney Diseases
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• v.1 no.1
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• pp.31-37
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• 1997

The DMSA scan is a useful radiologic study in diagnosis of morphologic and functional diseases of kidney. We evaluated the distribution of sex and age, clinical manifestations, diagnosis, combined diseases, treatment and prognosis of the 61 patients with non-functioning kidney(no isotope uptake or uptake below 5% in DMSA scan) who admitted in our hospital from 1980 to 1995. The proportion of patients under 1 year old age was 46%. Sex ratio was 1.4:1 with male predominance. Most diagnosis of non-functioning kidneys were congenital such as multicystic dysplastic kidney, hydronephrosis due to ureteropelvic junction obstruction, renal agenesis and renal hypoplasia. In order of frequency thirty one percent of them were previously detected on antenatal ultrasonogram. Treatment consisted of operation in 47.5%, mostly nephrectomy and 32.8% of patients were followed up at OPD base without definite treatment. The most common combined diseases was hydronephrosis, in 4patients who had both kidneys inveloved progressed to chronic renal failure, but the prognosis in most cases were good. It is important to evaluate renal diseases in perinatal periods, and we believe that highly sensitive diagnostic study contribute to early treatment plan and thus to good prognosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.5
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• pp.775-781
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• 2002

The T-type amino acid transporter 1 (TATI) is a Na$^{+}$-independent amino acid transporter which selectively trans- ports aromatic amino acids subserving the amino acid transport system T. To understand the transport properties of aromatic amino acids by human TAT1 (hTATl ), we have examined the hTATl -mediated aromatic amino acid transports using a Xenopus laeuis oocyte expression system. When expressed in Xenopin laeuis oocytes, hTATl induced L- [$^{14}$ C]tryptophan transport which was not dependent on Na$^{+}$ or Cl$^{[-10]}$ in the medium. Uptake was time-dependent and exhibited a linear dependence on incubation time up to 30 min. The L- ($^{14}$ C)tryptophan uptake was highly inhibited by L-isomers of tryptophan, tyrosine and phenylalanine, whereas other L-amino acids did not inhibit hTATl -mediated L- ($^{14}$ C)tryptophan uptake. The hTATl induced the relatively low-affinity transport of aromatic amino acids such as L- ($^{14}$ C)tryptophan, L- ($^{14}$ C)tyrosine and L- ($^{14}$ C)phenylalanine (Km values: 450～750 $\mu$M), consistent with the properties of classical amino acid transport system T. The L- ($^{14}$ C)tryptophan uptake did not show any remarkable pH dependence within the pH range of 5.5 to 8.5. The time-dependent efflux of L- ($^{14}$ C)tryptophan was detected from the oocytes expressing hTATl, which was not affected by the presence or absence of L-tryptophan in the extracellular medium, indicating that hTATl-mediated transport is due to the facilitated diffusion. Expression of hTATl in Xenopu laevis oocytes induced the transport of tryptophan, tyrosine and phenylalanine, indicating that hTATl is a transporter subserving system T These results suggest that hTATl has essential roles in the absorption of aromatic amino acids from epithelial cells to the blood stream. Hecause hTATl is proposed to be crucial to the efficient absorption of aromatic amino acids from intestine and kidney, its defect such as blue diaper syndrome could be involved in the disruption of aromatic amino acid transport.ort.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.21-26
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• 2002

Effects of cadmium (Cd) intoxication on renal endosomal accumulation of organic cations $(OC^+)$ were studied in rats using $^{14}C-tetraethylammnium$ (TEA) as a substrate. Cd intoxication was induced by s.c. injections of 2 mg Cd/kg/day for $2{\sim}3$ weeks. Renal cortical endosomes were isolated and the endosomal acidification (acridine orange fluorescence change) and TEA uptake (Millipore filtration technique) were assessed. The TEA uptake was an uphill transport mediated by $H^+/OC^+$ antiporter driven by the pH gradient established by $H^+-ATPase.$ In endosomes of Cd-intoxicated rats, the ATP-dependent TEA uptake was markedly attenuated due to inhibition of endosomal acidification as well as $H^+/TEA$ antiport. In kinetic analysis of $H^+/TEA$ antiport, Vmax was reduced and Km was increased in the Cd group. Inhibition of $H^+/TEA$ antiport was also observed in normal endosomes directly exposed to free Cd (but not Cd-metallothionein complex, CdMt) in vitro. These data suggest that during chronic Cd exposure, free Cd ions liberated by lysosomal degradation of CdMt in proximal tubule cells may impair the endosomal accumulation of $OC^+$ by directly inhibiting the $H^+/OC^+$ antiporter activity and indirectly by reducing the intravesicular acidification, the driving force for $H^+/OC^+$ exchange.

• The Korean Journal of Physiology
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• v.30 no.2
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• pp.279-288
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• 1996

Chronic exposure to cadmium impairs various renal tubular functions, including organic acid (anion) secretion. To investigate the mechanism of cadmium-induced alterations in the organic anion transport system, kinetics of p-aminohippurate (PAH) uptake was studied in renal cortical basolateral membrane vesicles (BLMV) isolated from cadmium-intoxicated rats (adult male Sprague-Dawley). Cadmium intoxication was induced by subcutaneous injections of $CdCl_{2}$ (2 mg Cd/kg per day) for 3 weeks. The renal plasma membrane vesicles were prepared by Percoll gradient centrifugation. The vesicular uptake of $^{14}C$-PAH was determined by rapid filtration technique using Millipore filter. Cadmium intoxication resulted in a marked attenuation of $Na^{+}$-dependent, ${\alpha}$-ketoglutarate (${\alpha}$KG)-driven PAH uptake with no changes in $Na^{+}$ and ${\alpha}$KG-independent transport component. Kinetic analysis indicated that Vmax, but not Km, of the $Na^{+}$-dependent, ${\alpha}$KG-driven component was reduced. A similar reduction of $Na^{+}$-dependent, ${\alpha}$KG-driven PAH uptake was observed in normal membrane vesicles directly exposed to inorganic cadmium in vitro, and this was accompanied by an inhibition of both $Na^{+}$-dependent ${\alpha}$KG uptake and ${\alpha}$KG-PAH exchange activity. These results indicate that during chronic exposure to cadmium, free cadmium ions liberated in the proximal tubular cytoplasm directly interact with the basolateral membrane and impair the active transport capacity for organic anions, most likely due to an inhibition of both $Na^{+}$-dicarboxylate cotransporter and dicarboxylate-organic anion antiporter activities.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.194-198
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• 2000

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of bio-logical activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But the taurine levles tend to increase in the brain in hypertensive state. In the present study, the blood-brain barrier (BBB) transport of [$^3$H]taurine was compared between spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD) using intravenous injection technique in vivo. We also obtained pharmacokinetic parameters of plasma volume maker, [$^{14}$ C] sucrose and [$^3$H]taurine after inject to rats simulatenously. BBB permeability surface area product (PS) value of [$^3$H]taurine in SHR (16$\pm$2.9$\times$10$^{-3}$ ml/min/g) was significantly higher than that in SD (7.4$\pm$0.8$\times$10$^{-3}$ ml/min/g). There is also significant difference for brain uptake of [$^3$H]taurine between SHR (0.195$\pm$0.031%ID/g) and SD (0.058$\pm$0.003% ID/g). This is due to difference of area under the plasma concentration-time curve (AUC) and that of total clearance (Class) between SHR and SD. No significant difference was indicated from other organ uptakes such as lung, heart, liver SHR and SD. But also kidney uptake was much higher in SHR. In conclusion, [$^3$H]taurine in plasma was slowly eliminated in SHR than in SD and uptake of [$^3$H]taurine in SHR is much higher than that of SD. This results suggest increased taurine level in the brain in hypertension state have an any effect on the brain uptake of taurine.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.2
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• pp.111-117
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• 2003

Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum(II) coordination complexes (PC-1 & PC-2) containing trans-${\iota}$ and cis-1,2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum(II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.2
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• pp.150-153
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• 2009

Xanthogranulomatous pyelonephritis is an uncommon chronic renal infection, which is usually found on middle-aged women and is rare in infant. Sometimes it forms focal mass like lesion of kidney with pathologically characteristic lipid-laden macrophage. A 1-month female infant was admitted for fever and moaning sound. On work-up of urinary tract infection, abdomen ultrasonography and computed tomography revealed a large mass on the upper portion of right kidney and PET/CT showed homogeneously increased $^{18}F$-FDG uptake. The radical nephrectomy of right kidney was performed and histology revealed a focal xanthogranulomatous pyelonephritis. To our knowledge, this is the first report presenting the finding of $^{18}F$-FDG PET/CT in the childhood xanthogranulomatous pyelonephritis.

• The Korean Journal of Nuclear Medicine
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• v.25 no.1
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• pp.95-100
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• 1991

Computerized scintigraphv using $^{99m}Tc-DTPA$ was performed to 37 isolated rabbit kidneys after preservation for 48 hours in perfusates differing in their compositions, i. e., Group 1 (N 9) in Collins' solution, Group 2 (N 10) in Collins' plus trifluoperazine, Group 3 (N 9) in Collins' plus urokinase and Group 4 (N 9) in Collins pius urokinase plus verapamil. Satisfactory images, and statistically analyzable quantitative indices such as perfusion score, filtration rate and cortical uptake ratio (CUR) were obtained by the evaluations of first-pass perfusion, equilibration slopes and postequilibration images. Significant improvements in CUR were observed by adding trifluoperazine (Group 2) and urokinase (group 3) as compared to Collins' only group (Group 1), p<0.05 for each, and all of the three indices (perfusion score, filtration rate and CUR) were also significantly (p=0.0092 p<0.05 and p<0.05) improved by adding urokinase plus verapamil (Group 4). We concluded that the computerized scintigraphy with Tc-99m DTPA provide valuable quantitative indices for evaluation of preserved kidney funcitions and suggest its possible clinical applicability in cadaver kidney transplantation considering the safety and easiness of the prodedure.