• 약학회지
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• 제44권2호
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• pp.149-154
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• 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.

• 한국약용작물학회지
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• 제25권4호
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• Advances in Traditional Medicine
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• 제4권1호
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• pp.22-27
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• 2004

Cisplatin is a highly effective and extensively used anticancer drug. Higher doses of cisplatin manifest acute nephrotoxicity and this is one of the limiting factors of this drug in cancer chemotherapy. The effect of the oyster mushroom extract to ameliorate cisplatin ( cis platinum (II) diammine dichloride) induced nephrotoxicity and restoration of antioxidant defence system in mice was investigated. The investigations showed that prior administration of methanolic extract of Pleurotus florida at a dose of 500 and 1000mg/Kg body weight significantly reduced elevated serum creatinine and urea levels and increased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the kidney, consequent to cisplatin treatment, in a dose dependent manner. The extract restored the decreased reduced glutathione (GSH) activity and increased malondialdehyde (MDA) level due to cisplatin administration. The results thus indicated that oyster mushroom extract rendered significant protection against cisplatin induced nephrotoxicity and depletion of antioxidant defence system in a dose dependent manner. Since oyster mushrooms are excellently edible and non-toxic, the finding reported here is of significant use in cancer chemotherapy.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.97-97
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• 2003

This study is investigated the effect of Rubus coreanus MIQ. against nephrotoxicity induced by cisplatin in rat. We examined the potency of the extract of R. coreanus fruits by the activity-guided fractionation. The EtOAc- and BuOH fraction, niga-ichigoside F$_1$and 23-hydroxytormentic acid showed significant protective effects as lipid peroxidation in renal tissue and was was not affect the activity of xanthine oxidase and aldehyde oxidase by cisplatin-induced nephrotoxicity. The concentration of glutathione in renal tissue was decreased by cisplatin-induced nephrotoxicity, but was improved by pretreatment of R. coreanus compounds especially in butanol, ethylacetate fraction and 23-hydroxytormentic acid.

• 생약학회지
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• 제29권3호
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• pp.258-264
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• 1998

Nephroprotective effects of a crude drug-preparation (Ekongsan) were determined from cisplatin induced renal injury in vivo and in vitro. Ekongsan decreased cisplatin induced the cytotoxicity on rabbit kidney proximal tubule and human renal cortical cells by MTT assays and sustained glucose consumption on cisplatin-induced human renal cortical tissue. Levels of creatinine and blood urea nitrogen (BUN) in serum after administration of cisplatin (0.75 mg/kg, i.p.) to Ekongsan (0.75 g/kg/d, p.o.) pretreated rats were markedly lower compared to those of cisplatin-treated rats. Moreover, the administration of Ekongsan significantly inhibited the loss of body weight of cisplatin-injected rats. These findings suggest that Ekongsan is an active prescription in protection against nephrotoxicity of cisplatin.

• 동의생리병리학회지
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• 제34권4호
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• pp.170-176
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• 2020

Palmijihwang-tang is an herbal formula frequently used to treat many symptoms, such as lumbago, pollakiuria, cold hands and feet, nephritis, sterilitas virilis, and prostatic disorders. The aim of this study was to investigate the effects of Palmijihwang-tang on cisplatin-induced nephrotoxicity in rat kidney proximal tubular NRK-52E cells. NRK-52E cells were treated with Palmijihwang-tang in absence or presence of 30 µM cisplatin for 12 or 24 h. Palmijihwang-tang at concentrations of 50-800 ㎍/ml did not change the cell viability in NRK-52E cells, and showed no significant toxicity. Palmijihwang-tang at concentrations of 400 and 800 ㎍/ml significantly increased the cell viability and reduced apoptotic cells in NRK-52E cells exposed to cisplatin. Also, Palmijihwang-tang markedly inhibited cisplatin-induced caspase-3 activation, PARP cleavage, ROS production and p53 activation in NRK-52E cells. Furthermore, Palmijihwang-tang did not interfere with the antitumor activity of cisplatin in AGS and A549 cancer cells. Particularly, Palmijihwang-tang enhanced antitumor activity of cisplatin in A549 cells. Taken together, these results suggest that Palmijihwang-tang ameliorated cisplatin-induced nephrotoxicity through reduction of ROS production and p53 activation, and did not interrupt antitumor efficacy of cisplatin against cancer cells.

• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.327-333
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• 1992

To evaluate the nephrotoxicity of cisplatin, serum levels of sodium, potassium, chloride, calcium, phosphorous, magnesium, BUN, creatinine and creatinine clearance were measured before and after administration of cisplatin in 18 cases of patients with malignant neoplasm. The results were as follows : 1) Serum calcium, magnesium, potassium and BUN levels were changed after cisplatin administration, but those changes were not statistically significant. 2) The mean value of creatinine clearance was not decreased significantly after treatment with cisplatin. 3) Acute renal failure was developed in one case, and four cases of hypocalcemia, hypomagnesemia were also detected after administration of cisplatin.

• 동의생리병리학회지
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• 제32권5호
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• pp.328-332
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• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1111-1114
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• 2013

Background: For early detection of renal damage during the usage of cisplatin based chemotherapy, changes in renal function should be monitored carefully. In recent years, neutrophil gelatinase-associated lipocalin, a small polypeptide molecule, has shown promise as a marker of acute renal failure. The aim of this present study was to assess possible risk prediction of cisplatin-induced nephrotoxicity using serum NGAL. Materials and Methods: A total of 34 consecutive patients with documented serum creatinine at least 24 hours before every cycle of cisplatin-based chemotherapy were included in the study. Demographic and medical data including age, performance status, tumor characteristics and comorbid diseases were collected from medical charts. Renal function was evaluated at least 48 hours before the treatment and at the end of the treatment based on the Modification of Diet in Renal Disease (MDRD) formula. Before and after cisplatin infusion serum NGAL levels were measured for the first and 3rd cycles of chemotherapy. Results: The median age of the study population was 54 (32-70) years. Fifteen patients (41.1%) were treated on an adjuvant basis, whereas 19 patients (58.9%) were treated for metastatic disease. There was no correlation of serum NGAL levels with serum creatinine (r=0.20, p=0.26) and MDRD (r=-0.12, p=0.50) and creatinine clearance-Cockcroft-Gault (r=-0.22, p=0.22) after cisplatin infusion at the end of the 3rd cycle of chemotherapy. Conclusions: In our study, serum NGAL levels were not correlated with the cisplatin induced nephrotoxicity. Further prospective studies are needed to conclude that serum NGAL level is not a good surrogate marker to predict early cisplatin induced nephrotoxicity.

• Biomolecules & Therapeutics
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• 제21권3호
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• pp.190-195
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• 2013

Cisplatin is a member of platinum-containing anti-cancer drugs that causes cross-linking of DNA and ultimately cancer cell apoptosis. The therapeutic function of cisplatin on various types of cancers has been widely reported but the side effects have been discovered together and nephrotoxicity has been regarded as major side effect of cisplatin. To select candidates for new sensitive nephrotoxicity biomarker, we performed proteomic analysis using 2-DE/MALDI-TOF-MS followed by cisplatin treatment in human kidney cell line, HK-2 cells, and compared the results to the gene profile from microarray composed of genes changed in expression by cisplatin from formerly reported article. Annexin A5 has been selected to be the most potential candidate and it has been identified using Western blot, RT-PCR and cell viability assay whether annexin A5 is available to be a sensitive nephrotoxic biomarker. Treatment with cisplatin on HK-2 cells caused the increase of annexin A5 expression in protein and mRNA levels. Over-expression of annexin A5 blocked HK-2 cell proliferation, indicating correlation between annexin A5 and renal cell toxicity. Taken together, these results suggest the possibility of annexin A5 as a new biomarker for cisplatin-mediated nephrotoxicity.