• YAKHAK HOEJI
• /
• v.44 no.2
• /
• pp.149-154
• /
• 2000

Flavin mononucleotide (1,4-butanediamine) Pt(II) complex (7FMN) was synthesized and screened anticancer activity [J. Pharm. Soc. Korea 43(6),762-770 (1999)]. 7FMN have good water solubility and moderate anticancer activiy In this paper cell-cycle specificity and nephrotoxicity were studied. Interaction of DNA with cisplatin and synthesized 7FMN was analyzed by flow cytometry and showed G2 arrest in L1210 cell line. It means that cell-cycle on L1210 was inhibit in S phase by cisplatin and 7FMN. In order to biochemically analyze nephrotoxicity of cisplatin and 7FMN, after injecting each agent intraperitoneally, blood was exsanguinated after 6 hours, 1 day, 3 days and 7 days, respectively. Then, serum was separated from the blood. The serum level of BUN, creatinine and uric acid in cisplatin and 7FMN administated mice (25~35 g, ICR strain, a dose each 8,12 and 16 times of the $IC_{50}$/ value, cisplatin; 7 times) were determined by autochemistry analyzer. In cisplatinadministered mice group, BUN level was elevated than normal control group at 3rd day and repaired at 7th day. In 7FMN administrated group was not elevated. Creatinine and uric acid level were no difference with the normal control group. Therefore synthesized 7FMN is less toxic than cisplatin in nephrotoxiciaty.

• 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.

• Asian-Australasian Journal of Animal Sciences
• /
• v.8 no.1
• /
• pp.7-11
• /
• 1995

Ethylene glycol was given orally in 6 crossbred male cow calves @ 12 ml/kg b wt for 2 days continuously to develop acute nephrotoxicity and monitor blood chemicals profile in affected calves. Progressive depression, hypersalivation, ataxia, incoordination, staggering gait, grinding of teeth, recumbency, coma, convulsions and death were prominent symptoms in affected calves. Respiration and pulse rates were increased whereas body temperature and rumen movements were low. Haematological investigations revealed increase in total erythrocyte count, platelets count and packed cell volume till death and total leukocyte count up to day 3 which decreased on day 4 and 5. These calves revealed azotaemia, reduction in calcium, chloride and potassium and rise in sodium and AST, ALT and alkaline phosphatase enzymes activity.

• Journal of Food Hygiene and Safety
• /
• v.8 no.4
• /
• pp.189-193
• /
• 1993

Cisplatin is useful for various cancers including advanced testicular and ovarian cancers. However, clinical use of cisplatin has been limited due to its dose-related neplrotoxicity. Transport studies across the membrane vesicles were performed to study the cisplatin nephrotoxicity. In these experiments, after cisplatin was administered to adult male New Zealand White rabbits, basolateral membrane (BLM) vesicles were prepared from the renal cortex. Para-aminohippurate (PAH) uptakes through BLM vesicles were measured to examine the interactioln of cisplatin on the transports of the substrates. As results of the uptake experiments using the vesicle systems, cisplatin had little effects on PAH transport through BLM vesicle. In conclusion, cisplatin did not cause the damage of basolateral membranes.

• Biomolecules & Therapeutics
• /
• v.3 no.4
• /
• pp.260-265
• /
• 1995

In an attempt to define the early biochemical determinants that participate in the pathogenesis of glycerol-induced nephrotoxicity, especially focusing on oxygen free radicals, we studied malondialdehyde (MDA) level and the activities of catalase and superoxide dismutase in the renal cortex of rats, and the concentrations of blood urea nitrogen(BUH) and serum creatinine of rats at 24hr after the injection of a 50% solution of glycerol. Sprague-Dawley albino rats weighing 240 to 260 mg were injected intramuscularly with a 50% solution of glycerol(2 mι/kg, 4 mι/kg and 8 mι/kg). The group treated with glycerol showed significantlv higher MDA level and catalase activity, lower SOD activity and higher BUN and serum creatinine concentrations at 24 hr after the injection as compared to those of control group. These results suggest that the excessive oxygen free radicals resulting from the depression of SOD activity is an important determinant in the pathogenesis of glycerol-induced nephrotoxicity.

• Toxicological Research
• /
• v.8 no.1
• /
• pp.95-107
• /
• 1992

Basolateral and brush border membrance (BLM and BBM) vesicles of renal proximal tubules were prepared from adult male New Zealand White rabbits to develop an experimental for assessment of nephrotoxicity. PAH uptakes using BLMV, and glucose and leucine uptakes using BBMV were measured in the rabbits treated uranyl acetate. In addition, urinalysis and histopathological studies were performed to investigate the correlationship with the membrance vesicle uptakes.

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2004.05a
• /
• pp.125-125
• /
• 2004

• Korean Journal of Clinical Pharmacy
• /
• v.16 no.2
• /
• pp.131-138
• /
• 2006

Heptaplatin, a new platinum derivative, has several contradicting reports on the nephrotoxicity. Therefore, the aim of this study is to compare the toxicities of heptaplatin-containing regimens in the chemotherapy. This study was performed retrospectively on seventy-seven patients with advanced gastric cancer who did not receive chemotherapy within the last 1 months before taking of heptaplatin- or cisplatin-containing chemotherapy. The 38 patients among total patients was received heptaplatin-containing regimens (26 with SEF regimens: heptaplatin/epirubicin/5-FU, 12 with SF regimens: heptaplatin/5-FU) and the rest 39 patients was received cisplatin-containg regimens (11 with CEF regimens: cisplatin/epirubicin/5-FU, 28 with ELF regimens: epirubicin/leucovorin/5-FU). Before and after the chemotherapy serum creatinine (Scr) and proteinuria were measured by urine stick test in all patient groups. Also Scr was measured a day before the second cycle and did not vary significantly between groups. However Scr on cycle 3 were significantly higher in SEF and SF groups. In case of proteinuria, it was more frequent on cycle 1 in heptaplatin/5-FU group. Proteinuria before and after on cycle 2 was not different between the two cisplatin -containing groups, but was more frequent in heptaplatin-containing groups. The reason why the Scr measured was not so different could be because we excluded the patients who received only one cycle of heptaplatin and changed the regimen due to signs of nephrotoxcity. As the results nephrotoxicity such as protienuria was appeared to be more frequent with heptaplatin-treated patients. It suggests that the clinical consequences of the toxicity need to further evaluation and also the modalities to prevent or minimize nephrotoxicity of heptaplatin should be studied for future utilization of the drug.

• Korean Journal of Clinical Pharmacy
• /
• v.27 no.4
• /
• pp.207-213
• /
• 2017

Background: It is recommended to use aerosolized (AS) colistin in patients undergoing mechanical ventilation therapy as an adjunctive in the latest guidelines, in spite of high nephrotoxicity and limited studies. In this study, systematic reviews and meta-analyzes were conducted to evaluate the safety and efficacy of AS colistin in patients with ventilator-associated pneumonia Methods: Two authors independently searched related literature published from Pubmed and EMBASE until July 2016 and included a study comparing adjunctive AS colistin with intravenous (IV) colistin monotherapy. The primary outcome was the clinical response rate, the secondary outcome was the overall mortality, and nephrotoxicity. The publication bias was evaluated using the Egger's test. Results: Of the total 279 articles, nine were finally included in the final analysis. There was a significant difference between the adjunctive AS colistin group and the IV colistin monotherapy group for the treatment-response rate (odds ratio (OR), 1.56; 95% CI, 1.14-2.14; p = 0.005; $I^2=36%$), although there was no significant difference in overall mortality (OR, 0.77; 95% CI, 0.57-1.04; p = 0.09; $I^2=20%$). However, there was no significant difference between the two groups in nephrotoxicity (OR, 1.13; 95% CI, 0.74-1.74; p = 0.57; $I^2=4%$). Conclusion: The addition of aerosolized colistin to IV colistin monotherapy showed better results in terms of efficacy than IV colistin monotherapy and did not show any significant difference in terms of total mortality and nephrotoxicity. Additional large-scale studies of this need to be verified.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.32 no.5
• /
• pp.328-332
• /
• 2018

In this study, Banhasasim-tang extracts (BSTE) have an inhibitory effects on cisplatin-induced nephrotoxicity in mouse model. Cisplatin is the most widely used anticancer drug for treatment of various cancer. However, cisplatin treatment to cancer patients leads to many side effects such as nephrotoxicity and body weight decrease. We hypothesize that BSTE improve the cisplatin-induced side effects in mouse model. We found that BSTE administration protected tubular injury by cisplatin in mouse model. BSTE also inhibited increase of creatinine and BUN induced by cisplatin injection in serum. Collectively, our data suggest that BSTE could be a therapeutic agent for reducing kidney injury induced by cisplatin treatment in cancer patients.