• Biomolecules & Therapeutics
• /
• v.20 no.3
• /
• pp.268-272
• /
• 2012

Nephrotoxicity occurs when kidney-specific detoxification and excretion do not work properly due to the damage or destruction of kidney function by exogenous or endogenous toxicants. Exposure to drugs often results in toxicity in kidney which represents the major control system maintaining homeostasis of body and thus is especially susceptible to xenobiotics. Understanding the toxic mechanisms for nephrotoxicity provides useful information on the development of drugs with therapeutic benefits with reduced side effects. Mechanisms for drug-induced nephrotoxicity include changes in glomerular hemodynamics, tubular cell toxicity, inflammation, crystal nephropathy, rhabdomyolysis, and thrombotic microangiopathy. Biomarkers have been identified for the assessment of nephrotoxicity. The discovery and development of novel biomarkers that can diagnose kidney damage earlier and more accurately are needed for effective prevention of drug-induced nephrotoxicity. Although some of them fail to confer specificity and sensitivity, several promising candidates of biomarkers were recently proved for assessment of nephrotoxicity. In this review, we summarize mechanisms of drug-induced nephrotoxicity and present the list of drugs that cause nephrotoxicity and biomarkers that can be used for early assessment of nephrotoxicity.

• Biomolecules & Therapeutics
• /
• v.2 no.2
• /
• pp.103-107
• /
• 1994

Cisplatin is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. Therefore, brazilin, which has a radical scavenging effect, was given intraperitoneally to evaluate the effect on cisplatin nephrotoxicity in rats. Remarkable protective effects against nephrotoxicity of cisplatin were observed when brazilin was administered to rats simultaneously with cisplatin. Hepatotoxicity induced by combination treatment of cisplatin and brazilin was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of sGPT and SGOT, and any combination treatment did not induce metallothionein in kidney. Brazilin which has radical scavenging effect directly reduced nephrotoxicity of wisplatin in vivo. Thus, it seems that nephrotoxicity of cisplatin was caused by free radicals. The present results Indicate that brazilin, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity in rats.

• Environmental Analysis Health and Toxicology
• /
• v.14 no.1_2
• /
• pp.13-19
• /
• 1999

Cisplatin is an inorganic complex formed by a central atom of platinum surrounded by chlorine and ammonia atoms in the cis position in the horizontal plane, Cisplatin is one of the most effective anticancer drug, widely used against various tumor such as testicular tumor, brain tumor, ovary tumor, bladder carcinoma, colon cancer etc. However its clinical use has been limited by nephrotoxicity, ototoxicity , gastrointestinal disturbances, myeloscrppression and allergic reactions. In these toxicities, dose related and cumulative nephrotoxicity is the major dose limit factor. So, to evaluate the protective effect of aspalactone on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally, Protective effects of aspalactone against nephrotoxicity of cisplatin were observed when aspalactone was administered to rats 1hr beforecisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and aspalactone was not observed. The present results indicate that aspalactone may provide protection against cisplatin nephrotoxicity, when it is given 1hr before cisplatin injection.

• Biomolecules & Therapeutics
• /
• v.1 no.1
• /
• pp.44-49
• /
• 1993

cis-Dichlorodiammineplatinum(cisplatin) is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. So, to evaluate the effects of 2(3)-tert-butyl-4-hydroxyanisole(BHA) on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally. Remarkable protective effects of BHA against nephrotoxicity of cisplatin were observed when BHA was administered to rats 1hr after cisplatin injection. On the other hand pretreatment with BHA 1hr prior to cisplatin did not reduce weight loss, blood urea nitrogen and creatinine levels. Hepatotoxicity induced by combination treatment of cisplatin and BHA was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of SGPT and sGOT except 1hr pretreatment. The present results indicate that BHA may provide protection against cisplatin nephrotoxicity, when it is given 1hr after cisplatin.

• BMB Reports
• /
• v.49 no.5
• /
• pp.288-292
• /
• 2016

Cisplatin is a platinum-based chemotherapeutic drug for treating various types of cancers. However, the use of cisplatin is limited by its negative effect on normal tissues, particularly nephrotoxicity. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and apoptosis are involved in the adverse effect induced by cisplatin treatment. Several studies have suggested that neuropeptide Y (NPY) is involved in neuroprotection as well as restoration of bone marrow dysfunction from chemotherapy induced nerve injury. However, the role of NPY in chemotherapy-induced nephrotoxicity has not been studied. Here, we show that NPY rescues renal dysfunction by reducing the expression of pro-apoptotic proteins in cisplatin induced nephrotoxicity through Y1 receptor, suggesting that NPY can protect kidney against cisplatin nephrotoxicity as a possible useful agent to prevent and treat cisplatin-induced nephrotoxicity.

• Korean Journal of Clinical Pharmacy
• /
• v.27 no.1
• /
• pp.22-29
• /
• 2017

Objective: Infection is very common in the elderly, so there is a high prevalence of antibiotics use among this population. Especially, due to the emergence of resistant bacteria, the use of vancomycin is growing. The purpose of this study was to evaluate risk factors associated with vancomycin-induced nephrotoxicity in elderly patients. Methods: The subjects of this study were patients over 18 years old who received intravenous vancomycin in a general hospital located in Gangneung-si, Korea between August 1, 2013 and July 31, 2015. Data collection regarding vancomycin use and baseline characteristics was conducted using computerized hospital database. Logistic regression analysis was used to identify risk factors associated with vancomycin-induced nephrotoxicity. Results: A total of 290 patients were finally included, and 191(66%) out of these patients were age 65 or older. The incidence of vancomycin-induced nephrotoxicity was 11.0%, 12.6%, and 7.0% in the all adult patients, the elderly patients, and the non-elderly patients, respectively. There were significant differences in comorbidities between patients with nephrotoxicity and patients without nephrotoxicity in the all adult patients, and there were significant differences in vancomycin duration, comorbidities, and number of nephrotoxic agents between patients with nephrotoxicity and patients without nephrotoxicity in the elderly patients. However, according to the logistic regression analysis, there was no significant risk factor that increases the incidence of vancomycin-induced nephrotoxicity in all three age groups. Conclusion: There were no differences in risk factors that increase the incidence of vancomycin-induced nephrotoxicity between all adult patients, elderly patients, and non-elderly patients. Further studies with larger sample sizes to identify risk factors associated with vancomycin-induced nephrotoxicity in the elderly to improve the outcome of pharmacotherapy are required.

• Molecular & Cellular Toxicology
• /
• v.2 no.3
• /
• pp.193-201
• /
• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• YAKHAK HOEJI
• /
• v.38 no.6
• /
• pp.627-636
• /
• 1994

Several Pt(II) and Pt(IV) complexes of N,N'-bis(2-hydroxyethyl)ethylenediamine(2-HEen) and N,N'-bis(2-chloroethyl) ethylenediamine(2-CEen) as carrier ligand were prepared. Water soluble Pt complexes were also synthesized by modification of leaving groups. The cytotoxicity of these compounds against leukemia L1210 and P388 cell in vitro were examined. The Pt complexes containing 2-CEen showed more effective cytotoxicity than those containing 2-HEen. Through the nephrotoxicity tests on the primary cultured proximal tubular cells of rabbit kidney and human kidney cells in vitro, Pt complexes with 2-CEen showed higher than those with 2-HEen which were consistent with cytotoxicity but showed very low nephrotoxicity compared with cisplatin. Also the values of BUN and creatinine in serum of Pt complexes were reduced remarkably compared with cisplatin, therefore it can be concluded that new Pt complexes seems to have much lower nephrotoxicity than cisplatin.

• Archives of Pharmacal Research
• /
• v.17 no.1
• /
• pp.11-16
• /
• 1994

Cis-dichlorodiammineplatinum(II)(cisplatin) is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. To evaluate the effect or radical scavengers on cisplatin nephrotoxicity in rats, cisplatin and Vitamin C were given intraperitoneally. Remarkable protective effects of Vitamin C against nephrotoxicity of cisplatin were observed when Vitamin C was administered to rats 1hr before cisplatin injection. hepatotoxicity induced by combination treament of cisplatin and Vitamin C was evaluated by measuring serum glutamic pyruvate transmainase(sGPT) and serum glutamic oxalate transminase(sGOT). Combination treatment did not affect the levels of sGPT and sGOT, and any combination treatment did not induce metallothionein biosynthesis in kidny, Vitamin C which has radical scavenging effect induce metallothionein biosynthesis in kidney. Vitamin C which has radical scavenging effect directly reduced nephrotoxicity of cisplatin in vivo. Thus, it seems that free radical is the cause of cisplatin nepthrotoxicity. Also, combination treatment did not reduce anticancer activity of cisplatin. The present results indicate that Vitamin C, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity without reducing anticancer activity.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.2
• /
• pp.316-325
• /
• 2003

In this paper, the effect of Ganopoly(extracts of Ganoderma lucidum) and Ganopoly/C+(70% Ganopoly + 30% chitosan) on cisplastin-induced nephrotoxicity was investigated in Sprague-Dawley rats. A single dose of cisplastin(5 ㎎/㎏) kg) was administered intraperitoneally after pretreatment of saline, Ganopoly and Ganopoly/C+ for 7 days. The nephrotoxicity and renal function were manifestated by the changes of body weight, blood pressure, biochemical changes and solute in urine and plasma. After the treatment of CDDP(cis-dichlorodiamineplatinum), a significant elevation of kidney weight, serum urea, cretinine, urine volume for 24 hours, urine magnesium, and a severe or significant decrease in body weight, blood pressure, creatinine clearance, urine osmolarity, serum albumin, etc. The nephrotoxicity was further confirmed by a significant decrease in glutathione S-transferase(GSH) in urine and kidney homogenate, GSH, glutathione peroxidase(GSH-Px) and catalase in kidney tissue. And also the lipid peroxidation was significantly increased in kidney homogenate. These signs of nephrotoxicity was ameliorated by the pretreatment and consecutive administration of Ganopoly and Ganopoly/C+ for 14 days after the Lp. injection of CDDP on 7th day after pretreatment of Ganopoly and Ganopoly/C+. The amelioration of nephrotoxicity was evidenced by significant reduction in serum urea and creatinine concentration, and improvement of other index of renal function. And The activity of antioxidant enzymes were partially recovered in kidney tissue of rats treated by CDDP and the administration of Ganopoly and Ganopoly/C+. These results indicate the cispastin induced nephrotoxicity is due to an impairment of tubular reabsorption systems enhanced by necrosis of proximal tubule, and the Ganopoly and Ganopoly/C+ has a partial protective effect on nephrotoxicity induced by CDDP. The polysacchride of Ganoderma lucidum may improve the therapeutic index of nephrotoxicity induced by CDDP. However, it is needed to elucidate the mechanism for confirming the therapeutic effect.