• Toxicological Research
• /
• v.11 no.1
• /
• pp.103-108
• /
• 1995

Rat renal proximal tubule suspension was prepared from adult male Sprague Dawley rat (250-300g) by mechanical (non-enzymatical) method and evaluated as a pontential model for mechanistic studies and early screening of nephrotoxicity, using anionic antibiotics (cephaloridine). Cephaloridine (CPL) produced an increase in LDH release into media. This release results from decrease a proximal tubule cell viability and subsequently increase the permeability of cell viability and subsequently increase the permeability of cell membrane. Since loss of intracellular potassium and ATP into media is the sign of disruption of cell membrane, especially basolateral membrane (BLM), CPL induced proximal tubule cell compromise also appear be associated with BLM, maybe $Na^+-K^+$ ATPase. Also seen was significant depression in brush border membrane (BBM) ALP activity and no significantly increase in BBM GGT activities. The inhibition of typical anion, PAH accumulation (especially, CPL 5 mM) and cation, TEA (especially, 4hours incubation) were seen dose dependently. This is because of CPL accumulation in renal proximal tubule and increase of cytotoxicity.

• Biomolecules & Therapeutics
• /
• v.9 no.3
• /
• pp.209-217
• /
• 2001

This study was attempted to investigate on renal effect of ($\pm$)6-chloro-7,8-dihydroxy-1-phenol 2,3,4,5-tetrahydro-lH-3 benzazepine (SKF 81297), dopamine $D_1$ receptor agonist, in dog. SKF 81297, when gluten intravenously, produced diuretic action along with the increases of renal plasma flow (RPF), glomerular filtration rate (GFR), amounts of N $a^{+}$ and $K^{+}$ excreted into urine ( $E_{Na}$ , $E_{K}$) and osmolar clearance ( $C_{osm}$). It also decreased the reabsorption rates of N $a^{+}$ and $K^{+}$ in renal tubule ( $R_{Na}$ , $R_{K}$) and free water clearance ( $C_{H2O}$), whereas ratios of $K^{+}$ agonist N $a^{+}$ in urine and filtration fraction (FF) was not changed. SKF 81297, when administered into a renal artery, elicited diuresis both in experimental kidney given the SKF 81297 and control kidney not given, while the effect was more remarkable in experimental kidney than those exhibited in control kidney. SKF 81297 given into carotid artery also exhibited diuresis, the potency at this time, compared to those induced by intravenous SKF 81297, was magnusgreat. Above results suggest that SKF 81297 produces diuresis by both indirect action through changes of central function and direct action being induced in kidney. Central diuretic action is mediated by improvement of renal hemodynamics, but direct action by inhibition of electrolytes reabsorption in renal tubule.enal tubule. tubule.

• The Korean Journal of Physiology
• /
• v.30 no.2
• /
• pp.249-256
• /
• 1996

The effect of probenecid on the transport of tetraethylammonium (TEA) was studied in renal cortical slices and isolated membrane vesicles to investigate the interaction of organic anion with the organic cation transport system in proximal tubule. Probenecid reversibly inhibited TEA uptake by renal cortical slices in a dose-dependent manner over the concentration range of 1 and 5 mM. The efflux of TEA was not affected by the presence of 3 mM probenecid. Kinetic analysis indicated that probenecid decreased Vmax without significant change in Km. Probenecid inhibited significantly tissue oxygen consumption at concentrations of 3 and 5 mM. However, probenecid did not significantly reduce TEA uptake in brush border and basolateral membrane vesicles prepared from renal cortex even at a concentration as high as 10 mM. These results indicate that probenecid reduces TEA uptake in cortical slices by inhibiting tissue metabolism rather than by an interaction with the organic ration transporter.

• The Korean Journal of Physiology
• /
• v.25 no.2
• /
• pp.171-177
• /
• 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.

• Archives of Pharmacal Research
• /
• v.22 no.4
• /
• pp.367-371
• /
• 1999

Effects of several durgs on rabbit renal proximal tubules were examined for the applicability of renal dipeptidase (RDPase, EC 3. 4. 13. 11) release as a model system to study nephrotoxicity. The proximal tubule prepared by the method of Taub (1990) released RDPase spontaneously in the control experiment which was confirmed by Western blotting. RDPase was also released form cisplatin, lipopolysaccardie (LPS), and indomethacin-treated tubules. Gentamicin inhibited RDPase release in a concentration-dependent manner. This RDPase release system may not be a general model to screen nephrotoxicity but could be a useful source of RDPase purification in a simple and inexpensive way.

• The Korean Journal of Physiology
• /
• v.28 no.2
• /
• pp.203-214
• /
• 1994

Using the methods of stopped-flow and epifluorescence microscopy with entrapped fluorophore, membrane permeability of $NH_3$ and weak acids in liposomes, renal brush border (BBMV) and basolateral membrane vesicles (BLMV), and primary culture cells from renal proximal tubule was measured. Permeability coefficient (cm/sec) of $NH_3$ was $(2.9{\times}10^{-2}$ in phosphatidylcholine liposome $25^{\circ}C)$, $5.9{\times}10^{-2}$ in renal proximal tubule cell $(37^{\circ}C)$, $4.0{\times}10^{-2}\;and\;2.4{\times}10^{-2}$ in BBMV and BLMV $(25^{\circ}C)$, respectively. Formic acid has the highest permeability coefficient among the weak acids tested, which was $4.9{\times}10^{-3}$ in liposome, $5.0{\times}10^{-3}$ in renal proximal tubule cell, $9.1{\times}10^{-3}$ in BBMV and $3.8{\times}10^{-3}$ in BLMV. There was a linear relationship between external concentration of nonionized formic acid and initial rate of flux of formic acid in liposome, and the slope coincided with the value of permeability coefficient of formic acid measured in pH 7.0. These results show that techniques of stopped-flow and epifluorescence microscopy with entrapped fluorophore provide the precise method of measurement of very rapid transport of nonelectrolytes through membranes with the advantages of instantaneous mixing effect, good resolution time and easy manipulation.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.28 no.3
• /
• pp.663-669
• /
• 1999

The purpose of this study was to investigate the effects of vitamin E on the histochemical change of kidney tissue in diabetic rats. Sprague Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal and three STZ induced diabetic groups, which were subdivided into vitamin E free diet(DM 0E group), 40mg vitamin E per kg diet(DM 40E group) and 400mg vitamin E per kg diet(DM 400E group). Vitamin E level of normal group was 40mg per kg diet. Diabetes was exper imentally induced by intravenous injection of 55mg/kg of body weight of streptozotocin(STZ) in citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic states. The contents of thiobarbituric acid(TBARS) in kidney were increased 119%, 84% and 33% in DM 0E, DM 40E and DM 400E groups, respectively, compared to normal group. That of DM 400E group was decreased 39% compared to DM 0E group. Content of 2 microglobulin in urine in DM 0E, DM 40E, and DM 400E groups were increased by 248%, 181%, and 164%, respectively, compared to normal group. The diabetic groups showed the regressive lesion such as renal tubule, intumescence of epithelial cell, vacuolization. The results of the observation through electronic microscope showed the mitochondria shape of proximal tubule epithelial cell, irregular array, increase of ribosome, and irregular arrangement of small villosity, etc. These types of changes appeared severer in DM 0E group than in DM 400E group. These results indicate that the TBARS productions on kdney in STZ induced diabetic rats were increased, consequently those leaded to damage of renal tubule and minuteness structure. But a large quantity vitimin E supplementation was suppressed in TBARS production and improved in peroxidative damage of renal tissue so that relieved degenerative changes of renal tubule epithelial cell.

• The Korean Journal of Pharmacology
• /
• v.26 no.2
• /
• pp.161-166
• /
• 1990

Infusion of bradykinin (BK) into the renal arteries increases sodium excretion. However, it is not clear whether natriuresis results from the renal hemodynamic effects or from the direct effect on renal tubular sodium transport. Therefore, we examined the effects of BK on the transport-dependent oxygen consumption in the distal tubule (DT) and cortical collecting tubule (CCT) of deoxycorticosterone-treated rats. BK inhibited oxygen consumption in a dose-dependent way with a maximal reduction at $0.1\;{\mu}M$ BK. The inhibitory effect of BK was not present in the absence of sodium or in the presence of ouabain (1 mM). These data imply that the inhibitory effect of BK is restricted to the sodium transport-dependent oxygen consumption. We also investigated the relationship between the effect of BK on oxygen consumption and arachidonic acid metabolism. Mepacrine $(10\;{\mu}M)$, an inhibitor of membrane phospholipases, prevented the inhibitory effect of BK, but indomethacin (0.5 mM) didn't. These results suggest that BK decreases the sodium transport-related oxygen consumption in the rat DT and/or CCT, and that it may be mediated by products of enzymes other than cyclooxygenase.

• Journal of fish pathology
• /
• v.18 no.2
• /
• pp.119-124
• /
• 2005

Two species of myxosporean parasites - Parvicapsula anisocaudata and an unidentified myxosporean were found in the lumina of renal tubules and the tubular epithelium, respectively, from cultured olive flounder, Paralichthys olivaceus in Korea. The latter was also seen in interstitial tissue of spleen and interrenal gland of the head kidney. Group of pseudoplasmodia of P. anisocaudata were firmly attached on the epithelium of renal tubules through pseudopodia. In the renal tubule epithelium, a group of unidentified myxosporean trophozoites, which were 2-3 times larger than intraluminal trophozoites of P. anisocaudata, was observed. The parasites being burst out into the lumen was occasionally encountered with partial break of the epithelium. Although infection of P. anisocaudata and unidentified myxosporean parasites did not induce any cellular reaction of the host, occlusion of renal tubules and rupture of renal epithelium would impact negatively on the renal functions of severely infected fish.

• The Korean Journal of Physiology
• /
• v.29 no.1
• /
• pp.69-80
• /
• 1995

Renal proximal tubular hypertrophy and hyperfunction are known to be early manifestations of experimental and human diabetes. As the hypertrophy and hyperfunction have been suggested to be central components in the progression to renal failure, an understanding of their underlying causes is potentially important for the development of therapy. A primary rabbit kidney proximal tubule cell culture system was utilized to evaluate the possibility that the renal proximal tubular hypertrophy and hyperfunction observed in vivo in diabetes mellitus, can be attributed to effects of elevated glucose levels on membrane transport systems. Primary cultures of rabbit proximal tubules, which achieved confluence at 10 days, exhibited brush-border characteristics typical of proximal tubular cells. Northern analysis indicated $2.2{\sim}2.3$ and 2.0 kb Na/glucose cotransporter RNA species appeared in fresh and cultured proximal tubule cells after confluence, repectively. The cultured cells showed reduced Na/glucose cotransporter activity compared to fresh proximal tubules. Primary cultured proximal tubule cells incubated in medium containing 20 mM glucose have reduced ${\alpha}-MG$ transport compared to cells grown in 5 mM glucose. In the proximal tubule cultures incubated in medium containing 5 mM or 20 mM glucose, phlorizin at 0.5 mM inhibited 0.5 mM ${\alpha}-MG$ uptake by 84.35% or 91.85%, respectively. The uptake of 0.5 mM ${\alpha}-MG$ was similarly inhibited by 0.1 mM ouabain (41.97% or 48.03% inhibition was observed, respectively). In addition, ${\alpha}-MG$ uptake was inhibited to a greater extent when $Na^{+}$ was omitted from the uptake buffer (81.86% or 86.73% inhibition was observed, respectively). In cell homogenates derived from the primary cells grown in 5 mM glucose medium, the specific activity of the Na/K-ATPase $(6.17{\pm}1.27\;{\mu}mole\;Pi/mg\;protein/hr)$ was 1.56 fold lower than the values in cell homogenates treated with 360 mg/dl D-glucose, 20 mM $(9.67{\pm}1.22\;{\mu}mole\;Pi/mg\;protein/hr)$. Total $Rb^{+}$ uptake occurred at a significantly higher rate (1.60 fold increase) in primary cultured rabbit kidney proximal tubule cell monolayers incubated in 20 mM glucose medium $(10.48{\pm}2.45\;nM/mg\;protein/min)$ as compared with parallel cultures in 5 mM glucose medium. $Rb^{+}$ uptake rate in 5 mM glucose medium was reduced by 28% when the cultures were incubated with 1 mM ouabain. The increase of the $Rb^{+}$ uptake by rabbit kidney proximal tubule cells in 20 mM glucose could be attributed primarily to an increase in the rate of ouabain-sensitive $Rb^{+}$ uptake $(5\;mM\;to\;20\;mM;\;4.68{\pm}0.85\;to\;8.38{\pm}1.37\;nM/mg\;protein/min)$. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Nafglucose cotransport system is inhibited.