• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.107-122
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• 2001

A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.98-98
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• 2001

It has been suggested that hyperuricemia is related to the development of essential hypertension. Hypertensive patients with hyperuricemia has decreased glomerular filtration activity as compared to normotensive patients with hyperuricemia. These studies indicates uric acid concentrations in blood is associated with hypertension, Probenecid is an uricosuric agent which decreases uric acid reabsorption at the proximal tubule. Recently, we have shown that probenecid exerts anti-hypertensive action in Spontaneously Hypertensive Rats. Considering these results, I have designed a series of experiments to explore potential mechanism of antihypertensive action, of probenecid. In isolated rat thoracic aorta. probenecid significantly prevented phenylephrine-induced contraction of the blood vessel. When endothelium removed blood vessels were used, probenecid produced same effect as the intact blood vessels, indicating that probenecid directly act through the ${\alpha}$ -adrenergic receptor in vascular smooth muscles rather than through endothelium. These results suggest that one of the mechanism of antihypertensive effects of probenecid is due to the direct inhibition of ${\alpha}$ -adrenergic receptor in blood vessels.

• Toxicological Research
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• v.17 no.4
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• pp.309-316
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• 2001

Male Sprague Dawley rats were exposed to 0, 0.04, 0.2, and 0.8% Pb acetate in drinking water for 13 weeks and fed a commercial diet. Dose-related adverse effects observed at the end of the Pb acetate exposure in the drinking water were as follows: decrease in body weight gain, decrease in hemoglobin, hematocrit(HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), increase in serum glucose, decrease in serum testosterone, increase in lead accumulation and $\delta$-ALA release in urine, and decrease in $\delta$-ALAD activities DNA content and histopathlogy (intranuclear inclusion body in kidney proximal tubule cell). Taken together, repeated exposure of lead acetate induced toxicities in hematopoietic system, especially testis and kidney.

• Childhood Kidney Diseases
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• v.27 no.2
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• pp.127-132
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• 2023

Cystinuria, a genetically inherited disorder, is a rare cause of kidney stones. It is characterized by impaired transport of cystine and amino acids in the proximal renal tubule and the small intestine. Most patients develop cystine stones throughout their lifetime. Recurrent renal stones need to be extracted by repeated urologic interventions. Treatment options of cystinuria for preventing stone recurrence are limited and poorly tolerated. In this study, we report a pediatric case of cystinuria with a heterozygous SLC3A1 mutation diagnosed by stone analysis, measurement of urine cystine excretion, and genetic analysis. There were recurrent renal stones despite repetitive shock wave lithotripsy and retrograde intrarenal surgery. However, the rate of stone formation seemed to be slower after D-penicillamine was added into adequate hydration and urinary alkalinization.

• Childhood Kidney Diseases
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• v.20 no.1
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• pp.11-17
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• 2016

Appropriate control of diet and water intake is important for maintaining normal blood pressure, fluid and electrolyte homeostasis in the body. It is relatively understood that the amount of sodium and potassium intake directly affects blood pressure and regulates ion transporters; Na and K channel functions in the kidney. However, little is known about whether diet and water intake regulates Aquaporin (AQP) function. AQPs, a family of aquaporin proteins with different types being expressed in different tissues, are important for water absorption by the cell. Water reabsorption is a passive process driven by osmotic gradient and water permeability is critical for this process. In most of the nephron, however, water reabsorption is unregulated and coupled to solute reabsorption, such as AQP1 mediated water absorption in the proximal tubule. AQP2 is the only water channel founded so far that can be regulated by hormones in the kidney. AQP2 expressed in the apical membrane of the principal cells in the collecting tubule can be regulated by vasopressin (antidiuretic hormone) controlling the final volume of urine excretion. When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane, leading to increased water absorption via this AQP2 water channel. However, some studies also indicated that the AQP2 is also been regulated by vasopressin independent mechanism. This review is focused on the regulation of AQP2 by diet and the amount of water intake on salt and water homeostasis.

• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.301-310
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• 1997

Diabetes mellitus is associated with a wide range of pathophysiological in the kidney. This study was designed to examine the effects of high glucose concentration on IGF-I binding and glucose transporters in renal proximal tubule cells. The results were as follows : The binding of $^{125}I-IGF-I$ reached the peak at the 30 minutes and gradually decreased by the time dependent manner. The binding of $^{125}I-IGF-I$ was inhibited by the unlabelled IGF-I($10^{-14}{\sim}10^{-8}M$) in a concentration dependent manner. The relative affinity of IGF-I receptor for IGF-I, IGF-II and insulin exhibited typical type 1 binding(IGF-I > insulin > IGF-II). However IGF-II did not compete for the cultured cell membrane $^{125}I-IGF-I$ binding site at $10^{-14}{\sim}10^{-8}M$. Under optimal conditions, IGF-I binding to the membranes from 5mM and 20mM glucose treated cells was analyzed. It was found that 20mM glucose treated cells exhibited higher binding activity for IGF-I. In order to further substantiate this increase in IGF-I binding sites, we performed affinity-labelling studies. The cross-linked cell membrane subjected to SDS-PAGE; labelled material was detected by autoradiography. 20mM glucose treated cells exhibited higher levels. The initial rate of $methyl-{\alpha}-D-glucopyranoside({\alpha}-MG)$ uptake was significantly lower($74.41{\pm}6.71%$) in monolayers treated with 20mM glucose than those of 5mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. IGF-I significantly increased ${\alpha}-MG$ uptake in both 5mM and 20mM glucose treated cells. However, 3-O-MG uptake was not affected by IGF-I in both conditions. In conclusion, 20mM glucose increased binding sites of $^{125}I-IGF-I$, inhibited Na/glucose cotransporter activity. But 20mM glucose did not change facilitated glucose transporter.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.283-295
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• 1993

Pt-complexes is currently one of the most compounds used in the treatment of solid tumors. However, its used is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogues containing 1, 2-diaminocyclohexane (dach) as carrier ligand and 1, 3-bis (diphenylphosphino) propane (DPPP)/1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of (KHPC-001) [Pt (trans-1-dach)(DPPP)] $2NO_3$ and (KHPC-002) [Pt (trans-1-dach)(DPPE)] $2NO_3$ were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. KHPC-001 and KHPC-002 demonstrated acceptable antitumor activity aganist P-388, L-1210 lymphocytic leukemia cells and significant activity as compared with that of cisplatin. The toxicity of KHPC-001 and KHPC-002 was found quite less than that of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells and human kidney cortical cells.

• Development and Reproduction
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• v.21 no.2
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• pp.193-204
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• 2017

The influence of triploidization on histological characteristics of retina, trunk kidney, liver and midgut tissue, and cell cycle of tail fin and gill tissue in far eastern catfish, Silurus asotus were analyzed. In the infertile triploid fish, the nucleus and/or cell size of secondary proximal tubule cells of trunk kidney, hepatocyte and midgut epithelium are much larger than those of the corresponding cells in the diploid fish (P<0.05). However, triploid tissue showed fewer number of outer nuclear layer in retina and nuclei in secondary proximal tubule of trunk kidney than those for diploid tissue. The mean percentages of the $G_l-$, the S- and the $G_2+M-phase$ fractions were 92.5%, 3.2% and 4.3% in tail fin tissue of diploid, and 93.4%, 2.6% and 4.0% in those of triploid, respectively. There were no significant differences in the percentages of each cell cycle fraction between diploid and triploid. The mean percentages of each phase fractions were 75.1%, 11.1% and 13.8% in gill tissue of diploid and 85.2%, 8.9% and 5.9% in those of triploid, respectively. The differences of cell cycle between tail fin tissue and gill tissue were statistically significant in diploid and triploid (P<0.05). Also, the differences between diploid and triploid were statistically significant in tail fin tissue and gill tissue (P<0.05). Cyclin D1 and cyclin E expressions were not significantly difference between gill tissue and tail fin tissue, and protein expressions of induced triploid were higher than those of diploid. Results from this study suggest that some characteristics in the triploid exhibiting larger cell and nucleus size with fewer number of cell than diploid can be used as an indicator in the identification of triploidization and ploidy level in far eastern catfish.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.7
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• pp.968-972
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• 2005

The purpose of this study was to evaluate the effects of chitosan, which is deacetylated derivative of chitin, on the renal function. Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) is glycosyl phosphatidyl-inositol (GPI)-anchored ectoenzyme of renal proximal tubular microvilli and was related with renal disease including acute renal failure, pyelitis and nephritis. The released RDPase and Udpase activities were assayed by modified fluorometric method. In vitro experimental groups were consisted of group 1, the concentration ranges of 0, 0.01, 0.05 and $0.1\%$ chitosan only, group 2, the concentration ranges of 1, 2 and 4 mM glycerol only, and group 3, the concentration ranges of 0, 0.01, 0.05 and $0.1\%$ chitosan in the presence of glycerol (4 mM). In vivo experimental groups were consisted of group 1 in which rats were treated with glycerol for the purpose of glycerol-induced renal damage, and group 2 in which rats were treated with chitosan plus glycerol. The RDPase release of 0.01, 0.05, and $0.1\%$ chitosan groups were increased in the concentration dependent manner. The RDPase release of 1, 2, and 4mM glycerol groups were decreased in the concentration dependent manner. Chitosan in the presence of glycerol restored the released RDPase activity in the proximal tubules. In vivo, chitosan inhibited the decrease of RDPase release by glycerol in the kidney and blocked the decrease of Udpase activity by glycerol in urine. These results indicated that chitosan was possible as a functional food to control renal function and its diseases.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.125-132
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• 1997

Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] . $2NO_3$ (PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $_{13}$carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ($^3$H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.