• Title/Summary/Keyword: Nephrotoxicity

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Development of a Novel Experimental Model for Nephrotoxicity Assessment Using Membrane Vesicles of Rabbit Renal Proximal Tubules (신장근위곡세뇨관 막소포를 이용한 신장독성 실험모델 개발)

  • 이영재;이창업;이문한;성하정;류판동
    • Journal of Food Hygiene and Safety
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    • v.8 no.4
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    • pp.195-204
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    • 1993
  • Basolateral and brush border membrane (BLM and BBM) vesicles of renal proximal tubules were prepared from adult male New Zealand White rabbits to evaluate as a potential model for assessment of nephrotoxicity. PAH uptakes using BLMV, glucose and leucine uptakes using BBMV were measured in the rabbits treated cephaloridine. In addition, urinalysis and histopathological studies were performed to investigate the correlationship with membrane vesicle uptakes. The results were as follows: (1) the activite of Na+, K+ -ATPase was enriched 12.3-fold in vasolateral memvrane vesicles (BLMV) and the specific activity of alkaline phosphatase in purified brush border memvrane vesicles (BBMV) was enriched 10.1-fold compared with each of microsomal homogenate. (2) In the uptake experiments, cephaloridine decreased initial and probenecid-sensitive PAH uptakes in BLMV. (3) Cephaloridine tested decreased initial and phlorizin-sensitive glucose uptakes in BBMV. (4) Cephaloridine tested decreased initial and Na+-dependent leucine uptakes in BBMV. (5) Cephaloridine tested significantly increased the urinary excretion of glucose and activity of ${\gamma}$-GTP. (6) Cephaloridine tested caused moderate necrotic changes in renal tubular cells and formation of urinary cast in the lumina of Henle's loop and collecting tubules besides the swelling of renal tubules.

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The role of testosterone on nephrotoxicity of mercuric chloride (Testosterone에 의한 승홍의 신독성 유발에 의한 연구)

  • Kim, Hoe-Young;Huh, Keun;Kim, Seok-Hwan;Choi, Jong-Won
    • Journal of Environmental Science International
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    • v.2 no.1
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    • pp.51-60
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    • 1993
  • Mercuric chloride, inorganic compound, is one of the most important drugs that has been used in the field of argriculture, antisyphilitica and anticeptics, but it is not used clinically at present. We have studied the effect of testosterone on the mercuric chloride-induced nephrotoxicity. Renal lipid peroxide concentration of male rat treated with mercuric chloride was significantly increased in comparison with that of the female rat, it showed similar effects on testosterone pretreatment. Changes in renal catalase and gluta- thione peroxidase activities were not siginificantly different in testosterone-treated groups. But, renal xanthine oxidase and aldehyde oxidase activities of testrosterone-treated group given mercuric chloride significantly increased in comparison with that of the testoste- rone-treated alone. Animals treated with testosterone prior to mercuric chloride showed more severe damage on histological observations than those treated with testosterone only. Consequently, we suggest that the mercuric chloride-induced nephrotoxicity might be renal lipid peroxide generating enzyme system by testosterone.

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Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells

  • Han, Myoung-Sik;Han, Im-Ho;Lee, Dahae;An, Jun Min;Kim, Su-Nam;Shin, Myoung-Sook;Yamabe, Noriko;Hwang, Gwi Seo;Yoo, Hye Hyun;Choi, Suk-Jung;Kang, Ki Sung;Jang, Hyuk-Jai
    • Journal of Ginseng Research
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    • v.40 no.2
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    • pp.135-140
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    • 2016
  • Background: Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods: The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results: The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNKep53ecaspase-3 signaling cascade.

Protective Effect of Korean Red Ginseng Against Dichromate Toxicity

  • Kim, Eun;Hyun, Hak-Chul;Na, Ki-jung
    • Proceedings of the Ginseng society Conference
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    • 1990.06a
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    • pp.132-136
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    • 1990
  • The metabolic disturbance and nephrotoxicity induced by sodium dichromate (20 mg/kg, SC) have been diminished by the administration of Korean red ginseng extract (100 mg/kg, PO). Red ginseng has a powerful potency on the blood urea nitrogen (BUN) increment shown in the early 2h after dichromate intoxication. It normalized the dichromate induced hepatic glycogenolysis. The effect of red ginseng on dichromate induced nephrotoxicity was investigated by hematological analysis, and urinalysis. Ginseng treatment significantly reduced the increases in the urinary excretion of protein and glucose. These effects were dose dependent. Ginseng protected the accumulation of BUN and cretonne in the blood, caused by dichromate intoxication. Unlike CaEDTA, ginseng did not change the urinary excretion chromium. And it could not convert htxavalent chromium to trivalent chromium. These results suggest that ginseng treatment is effective in decreasing the metabolic disturbance, one of the earliest signs of dichromate toxicity, resulting in the protective effect of dichromate induced renal damage.

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Antipseudomonal Activity and Nephrotoxicity of Cephradine-Netilmicin Combination

  • El Emam, M.A.;El Naggar, W.A.;Ibrahiem, T.M.
    • Archives of Pharmacal Research
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    • v.12 no.2
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    • pp.114-118
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    • 1989
  • The effects of intraperitoneal injection of cephradine in a dose of 75 mg/kg and netilmicin in dose of 50 mg/kg and their combination on creatinine and urea serum levels of rabbits were studied as well as the antipseudomonal activity against three multiresistant clinicial isolates. The antibacterial activity was investigated by two methods: Checkerboard titration method and time-kill studies. Finally, the antibacterial activity of the sera obtained from the rabbits receiving the used drugs in the previous regimen was studied using time-kill study method against Pseudomonas aeruginosa isolates. Results obtained from this study indicated that both creatinine and urea serum levels of the rabbits receiving both drugs were not significantly different from those of the rabbits receiving either cephradine or netilmicin alone. At the same time the in vitro antibactrial activity (either of the prepared solutions of the used drugs and their combination or of the sera obtained from the rabbits receiving these drugs as mentioned before) showed a synergistic effect against the tested strains of Pseudomonas aeruginosa

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Synthesis, Properties, and Application of Dithiocarbamate for Rescue of cis-[$Pt(NH_3)_2Cl_2$] Nephrotoxicity in Rats and Growth of Bacillus subtilis (흰쥐의 cis-[$Pt(NH_3)_2Cl_2$ 신장독성 회복과 Bacillus subtilis의 증식을 위한 디티오카바메이트의 합성, 성질 및 응용)

  • 이우식;김찬우;김인식;김창수
    • Journal of Environmental Health Sciences
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    • v.20 no.3
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    • pp.31-38
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    • 1994
  • Dithiocarbamates containing polar groups which give very water soluble metal complexes were prepared from the reaction of carbon disulfide with diamines. The compounds have been characterized by elemental analysis, molar conductivity, and spectroscopic results. Dithiocarbamate and its complex were soluble in water. N, N-Dimethylammoniumpropylenedithiocarbamate(A) is clearly effective as inhibition of cis-platinum nephrotoxicity in rats. From the result of A rescue after cis-dichlorodiammineplatinum(II) treatment, it is suggested that dithiocarbamate removes platinum(II) coordinated to -SH groups bound to protein of kidney tubule cells by the reaction of platinum(II) with dithiocarbamate injected. A is effective as antidots for acute cadmium poisoning in Bacillus subtills. Growth of Bacillus subtills may be accelerated by A ligand dissociated from cadmium (II)-A complex.

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Protective Effect of Korean Red Ginseng Against Dichromate Toxicity (중크롬산 독성에 대한 고려홍삼의 방어효과)

  • Kim, Eun;Hyun, Hak-Chul;Na, Ki-Jung
    • Journal of Ginseng Research
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    • v.14 no.2
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    • pp.274-278
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    • 1990
  • The metabolic disturbance and nephrotoxicity induced by sodium dichromate (20 mg/kg, SC) have been diminished by the administration of Korean red ginseng extract (100 mg/kg, PO). Red ginseng has a powerful potency on the blood urea nitrogen (BUN) increment shown in the early 2h after dichromate intoxication. It normalized the dichromate induced hepatic glycogenolysis. The effect of red ginseng on dichroamte induced nephrotoxicity was investigated by hematological analysis, and urinalysis. Ginseng treatment significantly reduced the increases in the urinary excretion of protein and glucose. These effects were dose dependent. Ginseng protected the accumulation of BUN and creatinine in the blood, caused by dichromate intoxication. Unlike CaEDTA, ginseng did not change the urinary excretion of chromiilm and it could not convert hexavalent chronlium to trialvalent chromium. These results suggest that ginseng treatment is effective in decreasing the metabolic disturbance, one of the earliest signs of dichromate toxicity, resulting in the protective effect of dichromate induced renal damage.

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Pharmacokinetic and Pharmacodynamic Characteristics of Cyclosporin A in Rats and Rabbits

  • Lee, Yong-Bok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.214-217
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    • 2002
  • Cyclosporin A (CSA) is a poorly water-soluble cyclic peptide comprising 11 amino acids. It inhibits T-lymphocyte function that plays an important role in the induction of immune response. The potent immunosuppressive activity of CSA has been used for the prevention of rejection following transplantation of liver, kidney and bone marrow, etc. The use of CSA has been often limited by several disadvantages including low bioavailability, narrow therapeutic window, nephrotoxicity, hepatotoxicity and neurotoxicity. Moreover, CSA injection is limited to patients who are unable to take the oral preparations, because it has a risk of anaphylactic shock and nephrotoxicity due to Cremophor EL$\textregistered$, a solubilizing agent used in the commercial intravenous formulation. Owing to above mentioned disadvantages of commercial products, there is a great interest in the development of the alternative dosage forms. (omitted)

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INFLUENCE OF OCHRATOXIN A-INDUCED NEPHROTOXICITY ON THE PHARMACOKINETICS OF GENTAMICIN IN RATS

  • Son, Deok-Soo;Han, Sang-Seop
    • Toxicological Research
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    • v.7 no.1
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    • pp.37-46
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    • 1991
  • To evaluate the influence of ochratoxin A on the pharmarcokinetics of gentamicin, gentamicin concentrations in the serum, renal cortex and medulla together with parameters of the renal function and histological changes were compared between ochratoxin A-treated rats (0.1 mg of ochratoxin A/kg of body weight, ip, daily for 14 days) and normal rats. Gentamicin was given with a single intramuscular injection (10mg/kg of body weight). Ochratoxin A resulted in an increase of the half-life, the area under the concentration-time curve, the apparent volume of distribution and a decrease of the total body clearance of gentamicin, and accumulated significantly (p<0.01) more gentamicin in the kidneys.

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Coumarins from the Roots of Angelica decursiva-albiflora (개바디 뿌리의 쿠마린성분)

  • Jung, Nam-Il;Yook, Chang-Soo;Lee, Hyeong-Kyu
    • Korean Journal of Pharmacognosy
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    • v.25 no.4 s.99
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    • pp.311-318
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    • 1994
  • From the root of Angelica decursiva-albiflora Yook, which has been used as a folk medicine for a sedative, analgesic and expectorant, four free coumarins, e.g., decursidin(I), decursin(II), umbelliferone(III) and nodakenetin(IV), and two coumarin glycosides, e.g., nodakenin(V) and decuroside I(VI) were isolate. The cytotoxicity of nodakenin(V) against L-1210 leukemia cells was less effective than cisplatin, but in the nephrotoxicity against rabbit kidney proximal tubular cell nodakenin(V) showed remarkably less nephrotoxicant than cisplatin.

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