• Archives of Pharmacal Research
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• v.20 no.4
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• pp.358-362
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• 1997

Metabolite identification and urinary and biliary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1 -piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid, hydrochloride] after oral administration have been studied in Sprague-Dawley rats. The excretion kinetics were monoexponential. Most of the drug was eliminated via the hepatic and renal routes. Mean renal clearance of DW116 was 73.4 ml/hr/kg and mean biliary clearance was 83.8 ml/hr/kg. The major metabolite excreted in the bile was identified as the glucuronide ester of the parent drug using base-hydrolysis of the conjugate metabolite followed by co-HPLC with standard compound, $^{19}$ F-NMR and LC-MS methods. The glucuronide conjugate was also found in urine. The mean urinary recoveries of free and total (free plus glucuronide ester) DW116 were $28.6{\pm}2.7% $and $36.4{\pm}1.8%$ of the administered dose and the corresponding biliary recoveries were $14.4{\pm} 5.5%$ and $37.0{\pm}7.6%$, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.4
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• pp.223-228
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• 2010

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B ($ET_BR$) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of $ET_BR$ increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal $ET_BR$ synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

• YAKHAK HOEJI
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• v.31 no.6
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• pp.376-393
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• 1987

This study was performed in order to investigate the effect of nifedipine, a vasodilating drug which acts through calcium antagonism, on renal function using mongrel dog. Nifedipine, when given interavenously in doses ranging from 1.5 to 5.0$\mu\textrm{g}$/kg, elicited diuresis along with less changes of glomerular filtration rate and significant increases of renal plasma flow, so that the filtration fraction(FF) decreased significantly, at the same time both osmolar and free water clearances increased, and amount of sodium, potassium and calcium excreted in urine increased significantly. Nifedipine, when infused into a renal artery in doses from 0.05 to 0.15$\mu\textrm{g}$/kg/min, exhibited identical responses to the actions of intraveneous nifedipine except significant increase of glomerular filtration rate and no change of FF, which was confined only to the infused kidney. The renal action of nifedipine into a renal artery were not influenced by renal denervation, decreased significantly by ouabain, Na$^+$-K$^+$-ATPase inhibitor, which was given into a renal artery. Nifedipine infused into a renal artery in dog pretreated with propranolol i.v. produced diuresis associated with the increase of electrolytes excretion by reduction of electrolyte reabsorption and with no changes of glomerular filtration rate and renal plasma flow. Thus, it is concluded that nifedipine infused into a renal aretery produces diuretic action along with both improvement of hemodynamics and inhibition of electrolytes reabsorption, which may be related to sympathetic $\beta$-receptor or Na$^+$-K$^+$-ATPase activity because the action of nifedipine in kidney is blocked by propranolol or ouabain.

• Toxicological Research
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• v.23 no.4
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• pp.289-299
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• 2007

Lipopolysaccharide (LPS) endotoxin is an active component in the outer membrane of Gram-negative bacteria. LPS is usually used as an inflammatory animal model. During the inflammation, diarrhea and changes in plasma proteins, in hepatic and/or intestinal microsomal cytochrome P450 (CYP) isozymes, and in the renal and/or biliary excretion of drugs have been reported. Thus, in rats pretreated with lipopolysaccharide endotoxin isolated from Klebsiella pneumoniae (KPLPS rats), the absorption, distribution, metabolism, and excretion of drugs could be expected to be altered. Interestingly time-dependent effects on the hepatic CYP isozymes have been reported in KPLPS rats. Thus, in KPLPS rats, the pharmacokinetics of drugs which are mainly metabolized via CYP isozymes could be expected to be time-dependent. In this review, an attempt to explain changes in pharmacokinetics of drug reported in the literature was made in terms of CYP isozyme changes or urinary and/or biliary excretion changes in KPLPS rats.

• YAKHAK HOEJI
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• v.22 no.4
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• pp.226-232
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• 1978

It was to investigate the absorption, excretion, protein binding of ampicillin in the pathological animals pretreated with carbon tetrachloride and mercuric chloride. The absorption of ampicillin was not affected in rats with damaged liver and kidney as compared with that of normal rats. The blood level of ampicillin after oral administration was increased significantly in rabbits with damaged kidney and liver. The blood level of ampicillin in rabbit with damaged kidney was more increased than that in rabbits with damaged liver. In severly damaged rabbits, it was more increased than that of mildly damaged rabbits. Urinary excretion of ampicillin in pathological animals was more inhibited than that of ampicillin in normals. Hepatic excretion of ampicillin was accelerated in rabbits with damaged kidney. However, in rabbits with damaged liver, it was inhibited as compared with that in normals. Protein binding of ampicillin was slightly enhanced by the various concentration of carbon tetrachloride and mercuric chloride, respectively. The results suggest that the increase of blood level of ampicillin in pathological animals was due to the inhibition of renal excretion.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.87-93
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• 2013

To evaluate the effect of the saponin of heat-processed ginseng (Sun ginseng, SG), we investigated the protective effect of SG total saponin fraction against adenine-induced chronic renal failure in rats. SG saponin significantly decreased the levels of urea nitrogen and creatinine in the serum, but increased the urinary excretion of urea nitrogen and creatinine, indicating an improvement of renal function. SG saponin also inhibited adenine-induced kidney hypertrophy and edema. SG saponin reduced serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase activities increased by adenine. Based on these findings, the ameliorating effect of SG on chronic renal failure may result from its saponin.

• Neonatal Medicine
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• v.17 no.2
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• pp.161-167
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• 2010

Acute kidney injury (AKI), formerly referred to as acute renal failure (ARF) is defined as the sudden impairment of kidney function (estimated from the glomerular filtration rate [GFR]) that results in the lack of excretion of waste products. More than 30 definitions of AKI exist in the literature, most of which are based on serum creatinine. Lack of a uniform and multidimensional AKI definition has led to failure to recognize significant renal injury, delays in treatment, and inability to generalize single-study results. The RIFLE criteria were developed to standardize the diagnosis of ARF and in the process the term AKI has been proposed to encompass the entire spectrum of the syndrome from minor changes in renal function to requirement for renal replacement therapy. Large prospective studies are needed to test definitions and to better understand risk factors, incidence, independent outcomes, and mechanisms that lead to poor short- and long-term outcomes. Early biomarkers of AKI need to be explored in critically ill neonates.

• Journal of Ginseng Research
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• v.36 no.3
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• pp.270-276
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• 2012

The effect of orally administered sun ginseng (SG), which is a ginseng processed by steaming, was examined in adenine-induced chronic renal failure rat. SG significantly decreased both blood urea nitrogen and serum creatinine levels, indicating an improvement of renal function. Also, SG significantly increased the urinary excretion of both urea and creatinine. Furthermore it lowered the blood pressure, and inhibited adenine-induced kidney hypertrophy and edema. Based on these findings, SG may ameliorate chronic renal failures.

• YAKHAK HOEJI
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• v.18 no.1
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• pp.39-48
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• 1974

Intravenously administered total water extract of Hoelen, (Pachymae fungus) in a dose of 10mg/kg and its methanol lextract, in a smaller dose than total water extract, produced significantly increase on urinary volume, sodium nad potassium excretion, and osmolar nad free water clearances. Increasing the doses produced more pronounced renal responses. Glomerular filtration rate and renal plasma flow changed littl with both extract. On the contrary, water extract from residue obtained on extraction with organic solvents exhibited no significant changes on the parameters of the renal function. In experiments, in which the total water extract was infused directly into a renal artery and urines from both ureters were collected separetely, a small dose of 0.3mg/kg/min showed no diuresis, but a large dose of 1.0mg/kg/min elicited diuretic action even on the contralateral kindneys. It is, therfore, concluded that Hoelen induces diuresis, mainly by inhibiting reabsorption of electrolytes in the renal tubules, and that the renotropic action may be mediated by some endogenous humoral substances.

• YAKHAK HOEJI
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• v.22 no.4
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• pp.207-214
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• 1978

Influence of Akebiae Lignum on the renal function of the dog was observed with water-extract, utilizing clearance technique. Akebiae Lignum water-extract (AWE) given intravenously in does of 3.0mg/kg and 30.0mg/kg elicited a marked antidiuretic effect and produced a distinguished decrease of glomerular filtration rate and renal plasma flow as reduction of sodium and potassium excretion in urine, positive free water clearance and osmolar clearance. AWE infused into a renal artery in doses of 0.03mg/kg/min and 0.1mg/kg/min exhibited identical results to the intravenous action confined only to the infused kidney. These results suggest that AWE elicits antidiuresis in the dog by decreasing glomerulor filtration and renal plasma flow, which are caused by the constriction of vas afferens in the glomeruli.