Abstract：
BACKGROUND:Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates p-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS:We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice. RESULTS:Vancomycin showed dose-dependent toxicity in the HK-2 cells, and cilastatin attenuated VIN. Vancomycin provoked the reactive oxygen species in a dose-dependent pattern on DCF-DA. Caspase 3/7 activity showed a dose-dependent increase at 6h. We confirmed apoptosis by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay at 24h (vancomcyin 2mM). Cilastatin attenuated vancomycin-induced ROS production and apoptosis, and it also attenuated vancomycin-induced P-gp suppression. In vivo, vancomycin (400mg/kg, 600mg/kg IP, 7days) induced acute kidney injury, as demonstrated by elevated blood urea nitrogen and creatinine. Histological examination of the sections indicated greater tubular damage in the vancomycin-treated kidney compared with the control. TUNEL-positive cells decreased significantly in the mouse kidney with cilastatin and vancomycin. Bax/Bcl-2 ratio were significantly increased in the vancomycin-treated kidney. Cilastatin 300mg/kg treatment significantly decreased the vancomycin concentrations in the blood and kidney. CONCLUSION:Our study showed that mechanism of VIN might be involved, at least in part, in suppressing P-gp function, and cilastatin attenuated VIN.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Im DS,Shin HJ,Yang KJ,Jung SY,Song HY,Hwang HS,Gil HWdoi
10.1016/j.toxlet.2017.05.023subject
Has Abstractpub_date
2017-08-05 00:00:00pages
9-17eissn
0378-4274issn
1879-3169pii
S0378-4274(17)30209-6journal_volume
277pub_type
杂志文章abstract：:The oxidation of styrene to styrene oxide and the hydration of this metabolite to styrene glycol was investigated in hepatocytes, 9000 x g supernatant (S9) and the microsomal fraction from rat liver. Similar amounts of free styrene oxide were found in microsomes, hepatocytes and S9. However, on the basis of the format...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(84)90120-6
更新日期：1984-11-01 00:00:00
abstract：:A diversity of chemicals cause discrete lesions in the kidney by a number of different mechanisms, and similar types of chemicals may give rise to more than one target cell injury. Screening for these lesions in vivo may be unreliable if a single noninvasive or invasive criterion is used. Instead, evidence of nephroto...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/0378-4274(89)90132-x
更新日期：1989-03-01 00:00:00
abstract：:The aim of this study was to determine the toxicokinetics and some effects of 1,1,1-trifluoroethane (HFC-143a) in humans. Nine male volunteers were experimentally exposed to 500ppm HFC-143a for 2h during light physical exercise (50W) in an exposure chamber. Blood, urine and exhaled air were sampled before, during and ...
journal_title：Toxicology letters
pub_type： 临床试验,杂志文章
doi：10.1016/j.toxlet.2007.05.010
更新日期：2007-08-01 00:00:00
abstract：:Hypoallergenic infant formulas are widely used for infants with cow's milk allergy. The aim of this study was to assess the utility of the mouse basophil activation test (BAT) in the evaluation of residual antigenicity in these formulas. Whole blood samples derived from β-lactoglobulin- or casein-immunized mice were i...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2015.11.024
更新日期：2016-02-03 00:00:00
abstract：:The lithocholic acid-sensitive mutant cells were isolated from CHO-9 cells mutagenized with ethylmethane sulfonate, through clonal selection on 96-well dishes. The isolated mutant cells (LSJ-11) were 3-fold more sensitive than controls in the survival to lithocholic acid and were also sensitive to other bile acids suc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(93)90001-e
更新日期：1993-03-01 00:00:00
abstract：:Sulphur mustard (SM) is a blistering agent that causes debilitating damage to the skin, eyes and respiratory system. In cases of severe exposure, immunodepletion can occur as well as death, due to secondary infections. The toxicity of SM is thought to be mediated in part by the alkylation of nucleic acids and proteins...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.11.009
更新日期：2012-02-25 00:00:00
abstract：:In order to gain basic understanding in the ecotoxicity of endocrine disrupting chemicals or EDCs (including natural chemicals and some pharmaceuticals), many international research groups are currently testing these chemicals using aquatic invertebrates. This paper discusses relevant examples to address key questions...
journal_title：Toxicology letters
pub_type： 杂志文章,评审
doi：10.1016/s0378-4274(02)00046-2
更新日期：2002-05-10 00:00:00
abstract：:Nonylphenol (NP) is a representative endocrine disruptor that has an adverse effect on male reproduction and posses direct hazard to Sertoli cells, but the mechanism remains incompletely elucidated. In the present study, based on the structural comparability and high affinity between NP and membrane phospholipid molec...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2008.08.011
更新日期：2008-12-15 00:00:00
abstract：:Methylglyoxal (MG) is a metabolite of glucose. The serum MG level is increased in diabetic patients, and MG is implicated in diabetic complications related to embryonic development injury. We previously reported cytotoxic effects of MG on mouse embryonic stem cells and blastocysts, and a further association with defec...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2010.01.007
更新日期：2010-04-01 00:00:00
abstract：:A number of retrospective studies have suggested that choice of anesthetic drugs during surgical tumor resection might affect tumor recurrence/metastasis, or outcome of patients. The recent study showed that volatile anesthetics-based general anesthesia was associated with the worse outcomes than intravenous anestheti...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2016.12.007
更新日期：2017-01-15 00:00:00
abstract：:Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially ex...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.11.019
更新日期：2018-03-01 00:00:00
abstract：:Spontaneous neoplasms in untreated control CD-1 mice (725 males and 725 females) used in carcinogenicity studies were evaluated and tabulated. The most common neoplasms in male mice were alveolar-bronchiolar adenomas (19.3%) followed by hepatocellular adenomas (11.0%), lymphoreticular neoplasms (6.8%), hepatocellular ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(92)90064-q
更新日期：1992-06-01 00:00:00
abstract：:Fe(3)O(4) magnetic nanoparticles (MNPs) coated with 2,3-dimercaptosuccinnic acid (DMSA) are considered to be a promising nanomaterial with biocompatibility. In the present study, the effects of DMSA-coated Fe(3)O(4) MNPs on the expression of all identified mouse genes, which regulate various cellular biological proces...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2011.05.1031
更新日期：2011-08-28 00:00:00
abstract：:Exposition to cadmium (Cd) has been linked to bone metabolism alterations and occurrence of osteoporosis. Despite its known renal toxicity which indirectly disrupts bone metabolism through impairment of vitamin D synthesis, increasing evidence argues for the direct action of Cd on bone-forming osteoblasts. Indeed, acc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.10.006
更新日期：2012-12-17 00:00:00
abstract：:The structural analogy of paraquat with 1-methyl-4-phenylpyridinium (MPP+) has been implied in the aetiology of Parkinson's disease. The cross-reactivity of MPP+ to a specific antibody to paraquat was assessed by radioimmunoassay and was found to be very low. The results suggest that this polyclonal paraquat antibody ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(90)90238-h
更新日期：1990-10-01 00:00:00
abstract：:Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is asso...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.12.006
更新日期：2013-03-13 00:00:00
abstract：:It has reported that many environmental compounds may display estrogenic actions and these findings led to researchers to associate breast cancer risk with the use of some pesticides. The aim of this work was to investigate the effect of chlorpyrifos (CPF) on cell proliferation and the ERα-dependence of this action em...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.06.017
更新日期：2012-09-03 00:00:00
abstract：:Mercury(II) ions are known to accumulate in the kidney and their effect upon the renin-angiotensin system has also been described. The question, however, whether mercury(II) also exerts direct effect on the juxtaglomerular cells (JGC) to induce renin release remained to be answered. Suspension of isolated glomeruli wa...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(96)03637-5
更新日期：1996-04-01 00:00:00
abstract：:Several in vivo and in vitro studies have assessed methods of evaluating the cardio toxicity of compounds during drug development due to its importance for predicting human toxicity. However, in vivo/in vitro relationships have not yet been reported using a zebrafish model. This study determined the bradycardia of 15 ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.10.018
更新日期：2013-01-10 00:00:00
abstract：:A model of the growing small animal skeleton has been developed. The model accurately reproduces a variety of different kinds of measurements made at different ages in different species, as well as reproducing a precise and detailed series of measurements in the growing guinea pig. Of the multiple mechanisms responsib...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90022-7
更新日期：1988-10-01 00:00:00
abstract：:We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological exa...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2004.03.018
更新日期：2004-08-01 00:00:00
abstract：:The effects of zinc on the lipid components of carp erythrocytes (Cyprinus carpio L.) were studied on red blood cells exposed to ZnSO4 (0.01-1 mM) for 20 h. The temperatures of the incubation medium were 5 and 20 degrees C for carp collected in winter and summer, respectively. It was observed that increase in the conc...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(02)00066-8
更新日期：2002-06-07 00:00:00
abstract：:Because coarse mode particles are rarely studied in their existing size ranges (greatest mass about 5-7 microns, aerodynamic diameter), we investigated the effects of four such particles, quartz, ferric oxide, calcium carbonate, and sodium feldspar, on host defenses against bacterial pulmonary infection. Mice which re...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(83)90263-1
更新日期：1983-10-01 00:00:00
abstract：:A toxicogenomics approach was applied to assess the usefulness of the mouse cytotoxic T cell line CTLL-2 for in vitro immunotoxicity testing. CTLL-2 cells were exposed for 6 h to two model immunotoxic compounds: (1) the mycotoxin deoxynivalenol (DON, 1 and 2 μM), a ribotoxic stress inducer, and (2) the organotin compo...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2012.12.005
更新日期：2013-02-13 00:00:00
abstract：:To clarify a possible mechanism of zinc (Zn)-induced tolerance to cadmium (Cd) toxicity on bone formation, femurs from 9-day-old chick embryos were cultured for 6 days by the roller-tube method in the presence of Cd (2, 4 or 9 microM) and/or Zn (60 microM). Zn prevented a decrease in bone growth caused by Cd at 4 and ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(88)90149-x
更新日期：1988-11-01 00:00:00
abstract：:Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight volatile cyclic siloxane, primarily used as an intermediate in the production of some widely-used industrial and consumer silicone based polymers and may be present as a component in a variety of consumer products. A global "harmonized" risk assessment was co...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2017.05.019
更新日期：2017-10-20 00:00:00
abstract：:A 13-week subchronic toxicity study of thiamphenicol (TAP) was performed in F344 rats. The minimum lethal dose was estimated to be greater than 10 g/kg body weight, when a single dose of 4-10 g/kg of TAP was given orally. In the subchronic toxicity study, groups of 12 F344 rats of each sex were given solutions contain...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(97)03883-6
更新日期：1997-04-28 00:00:00
abstract：:There have been many concerns about the possible adverse effects of thyroid hormone-disrupting chemicals in the environment. Because thyroid hormones are essential for regulating the growth and differentiation of many tissues, disruption of thyroid hormones during the neonatal period of an organism might lead to perma...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/j.toxlet.2018.01.005
更新日期：2018-04-01 00:00:00
abstract：:To reduce the production of pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE) and other ethers such as ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Metabolism of these gasoline ethers is catalyzed by cytochrome P450 ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/s0378-4274(98)00389-0
更新日期：1999-03-08 00:00:00
abstract：:Induction of endotoxin tolerance in rats led to reductions in bile flow and BSP excretion. BSP serum retention or storage of BSP in the liver was not affected. Although serum alanine aminotransferase (ALT) activity was slightly elevated in endotoxin-tolerant rats, the levels of serum aspartate amino-transferase (AST) ...
journal_title：Toxicology letters
pub_type： 杂志文章
doi：10.1016/0378-4274(82)90151-5
更新日期：1982-05-01 00:00:00
