Abstract:
:Polypeptide antibiotics, such as polymyxins and aminoglycosides, are essential for treatment of life-threatening Gram-negative infections. Acute kidney injury (AKI) attributed to treatment with these agents severely limits their clinical application. Because standard biomarkers (serum creatinine [sCRE] and blood urea nitrogen [BUN]) feature limited sensitivity, the development of novel biomarkers of AKI is important. Here, we compared the performance of standard and emerging biomarkers of AKI for the detection of nephrotoxicity caused by polymyxin B across multiple species (rat, dog and monkey). Further, we applied a biomarker-driven strategy for selection of new kidney-sparing polymyxin analogs. Polymyxin B treatment produced dose-dependent kidney injury observed as proximal tubular degeneration/regeneration and necrosis across all species. Dogs and monkeys had similar biomarker profiles that included increases of both standard (sCRE and BUN) and emerging (urinary neutrophil gelatinase-associated Lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) biomarkers of AKI. In contrast, only urinary NGAL and urinary KIM-1 were sufficiently capable of detecting kidney injury in rats. Because rats provide a feasible model for screening compounds in drug development, we utilized urinary NGAL as a sensitive biomarker of AKI to screen and rank order compounds in a 2-day toxicity study. To our knowledge, this study provides a first example of successfully applying biomarkers of AKI in drug development.
journal_name
Drug Chem Toxicoljournal_title
Drug and chemical toxicologyauthors
Burt D,Crowell SJ,Ackley DC,Magee TV,Aubrecht Jdoi
10.3109/01480545.2013.834360subject
Has Abstractpub_date
2014-04-01 00:00:00pages
204-12issue
2eissn
0148-0545issn
1525-6014journal_volume
37pub_type
杂志文章abstract::Butea monosperma (Lam.) Taub. is an ethnomedicinal tree of remedial value in the treatment of diabetes, bone fractures, and liver and neurological disorders. However, the information available on DNA-protective and anti-proliferative potential of bark of this tree is scarce. In the present study, the extract/fractions...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2018.1497051
更新日期:2020-07-01 00:00:00
abstract::As a measure of glutathione (GSH) conjugation, urinary, fecal and biliary excretion of thioethers and hepatic GSH content were measured in rhesus monkeys following administration of single doses of naphthalene and diethylmaleate (DEM). Naphthalene had little or no effect on hepatic GSH content and the excretion of thi...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480548209041057
更新日期:1982-01-01 00:00:00
abstract::For centuries, Turkey has been a significant location here around 80 species of Hypericum with differing names widely occur, which is also known as Turkish folk medicine in treating some bacterial diseases as well as stomach and intestine inflammation. Recent studies have reported this herb family to contain numbers o...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2020.1856130
更新日期:2020-12-06 00:00:00
abstract::The relationship between lead concentration in the dry film of lead based paints applied to steel bulkheads aboard ship, the lead concentration found in the air when the paint is removed by mechanical means, and blood lead concentrations of workers involved in lead based paint removal has not been well characterized. ...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549909029723
更新日期:1999-02-01 00:00:00
abstract::In May 1993, Administrative Browner of the U.S. Environmental Protection Agency (USEPA) announced that an indirect exposure health risk assessment was required for all hazardous waste combustion facilities seeking a Resource Conservation and Recovery Act permit. These types of risk assessments evaluate the health and ...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1081/dct-100100103
更新日期:2000-02-01 00:00:00
abstract::Understanding the mechanism behind neuronal regeneration is critical for treating ischemic stroke and traumatic brain injury. The presence of neural stem cells in and around the sub-ventricular zone of human and also in zebrafish is evidenced. In this current study, the neuro-protective potential of nano-formulated he...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2020.1722690
更新日期:2020-02-12 00:00:00
abstract::Effects of diazinon, at different concentrations and exposure times, were investigated in freshwater fish, Cyprinus carpio, to elucidate the possible mode of action on lipid peroxidation together with the inhibitory effect of diazinon on acetylcholinesterase activity and changes in tissue protein levels. Cholinesteras...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480540500408622
更新日期:2006-01-01 00:00:00
abstract::The responses of atria isolated from four groups of rats: (a) control (air/H2O) and test animals treated with (b) 5 PPM nitrogen dioxide NO2 for 72 hours, (NO2/H2O), (c) 10% ethanol (ET) in water for 13 days, (air/ET), or (d) combination of NO2 and ET (NO2/ET). Isolated atria were tested with norepinephrine and dose r...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480548309017818
更新日期:1983-01-01 00:00:00
abstract::In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by compari...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549509014323
更新日期:1995-11-01 00:00:00
abstract::Cisplatin (CP) is a widely used cytotoxic agent against cancer, and high doses of CP have been known to cause nephrotoxicity and hepatotoxicity. Some reports claim that antioxidants can reduce CP-induced toxicity. This study investigated the hepatoprotective, nephroprotective, and antioxidant activity of Urtica dioica...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480545.2011.598531
更新日期:2012-07-01 00:00:00
abstract::Eight antineoplastic drugs were evaluated for their ability to induce mutation in the Ames Salmonella/microsome and the TK+/- mouse lymphoma assay. Dose response data were utilized to determine the relative potency of each of these drugs. They were then ranked based on this information. Vincristine, the most potent co...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480547809105021
更新日期:1978-01-01 00:00:00
abstract::Visual observations were made to compare the pretreatment benefits of subacute (75 micrograms/hr, sc) and acute (146 micrograms/kg, im, at 30 min) deliveries of physostigmine salicylate (Phy) against 2 or 5 LD50s (60 or 150 micrograms/kg, sc) of soman in guinea pigs; scopolamine, 80 micrograms/kg, im, was given routin...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549109017866
更新日期:1991-01-01 00:00:00
abstract::Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1624767
更新日期:2019-06-14 00:00:00
abstract::This study investigated the exposure of pyrethroids in the development of Alzheimer's type neurodegeneration by analyzing β- amyloid, tau and Glial Fibrillary Acidic Protein (GFAP) in adult Wistar rats. Forty adult Wistar rats (130-150 g) of both sexes were assigned into five groups (n = 8). Groups A-C were treated wi...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2020.1778020
更新日期:2020-09-09 00:00:00
abstract::The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepam, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. All comp...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549209014150
更新日期:1992-01-01 00:00:00
abstract::Pyridoxal isonicotinoyl hydrazone (PIH) is a highly effective iron chelator. Acute toxicity testing was performed in mice and rats of both sexes, with 10 mice or rats/sex/group. The LD50 values of PIH in both species were 5 and 1 g/kg given orally and intraperitoneally, respectively. Microscopic examination of tissues...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549109011641
更新日期:1991-01-01 00:00:00
abstract::Currently, no standardized and well-validated alternative models exist for screening for progesterone-responsive endocrine disrupting chemicals (EDCs). Because of this, a rapid assay for evaluating progestin/antiprogestin activity using Xenopus oocyte germinal vesicle breakdown (GVBD) as a model was evaluated. Five co...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1081/dct-120005892
更新日期:2002-08-01 00:00:00
abstract::The effect of a novel phosphorothionate, the methyl ester of 2-butenoic acid-3-diethoxy phosphinothioyl (RPR-II) was studied on membrane bound target enzymes Acid (AcP) and Alkaline (AkP) Phosphatases in different tissues of male and female albino Wistar rats. Three sub-chronic doses 0.014 (low), 0.028 (medium) and 0....
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1081/dct-100100131
更新日期:2000-08-01 00:00:00
abstract::Cadmium (Cd) is a ubiquitous non-essential environmental and industrial toxicant that affects various organs in humans and experimental animals. Robust evidence confirms the contribution of oxidative stress to the pathogenesis of Cd-induced hepatic damage. Potent polyphenols found in virgin coconut oil (VCO) are free ...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1598428
更新日期:2019-04-25 00:00:00
abstract::Toxic fungal metabolites - mycotoxins - cause poisonings after consumption of contaminated food commodities. The most probable intoxications are connected with eating poorly stored food or inhaling of moldy dust. One of the effective ways to protect people against mycotoxins is timely detection. Several methods such a...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章,评审
doi:10.1080/01480540701375232
更新日期:2007-01-01 00:00:00
abstract:CONTEXT:Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, chang...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480545.2014.900073
更新日期:2015-01-01 00:00:00
abstract::Orlistat is an FDA-approved over-the-counter drug to treat obesity through the inhibition of lipase activity. Macrophages, which express high levels of lipoprotein lipase (LPL), are important phagocytes in the innate immune system. Our previous studies indicated that environmentally relevant concentrations of arsenite...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1683571
更新日期:2019-10-31 00:00:00
abstract::Aluminum (Al)-induced toxicity in fruit fly (Drosophila melanogaster) is one of the established models for studying neurotoxicity and neurodegenerative diseases. Alkaloid phytochemicals have been reported to exhibit neuroprotective effects. Therefore, the aim of this study is to determine the effect of alkaloid extrac...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1708377
更新日期:2020-01-03 00:00:00
abstract::Chronic exposure to solar ultraviolet (UV) light induces photoaging in human skin. Our previous results have shown that areca nut procyanidins (ANPs) have antioxidant capacity and possess potential anti-inflammatory effects. Here, we aimed to investigate the effect of ANPs on UVB-induced photoaging. In the present stu...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1696813
更新日期:2019-12-02 00:00:00
abstract::Experiments were carried out to ascertain whether or not saffron (dried stigmas of Crocus sativus L.), a commonly used agent for flavoring and coloring food can exert modulatory effects on the in vivo genotoxicity of cisplatin (CIS), cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE). For this purpose, Swiss...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1081/dct-100106266
更新日期:2001-11-01 00:00:00
abstract::As part of an occupational hazard evaluation, p-bromobenzyl bromide (p-BBB) was evaluated for genotoxic activity in the Ames microbial mutagenicity assay, the alkaline elution assay for DNA strand breaks in rat hepatocytes and the in vitro chromosome aberration assay in Chinese hamster ovary cells. The compound produc...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.3109/01480549908993169
更新日期:1999-11-01 00:00:00
abstract::Diterpene alkaloids (DAs) have a broad spectrum of pharmacological activities, but exhibiting extremely serious cardiotoxicity to induce arrhythmia, heart arrest, even death. This study aimed to evaluate the cardiotoxicity of three diester diterpene alkaloids (DDAs) including aconitine (AC), mesaconitine (MAC), hypaco...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2019.1586916
更新日期:2019-03-21 00:00:00
abstract::Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal transition (EMT) was a significant process in pulmonary fibrosis. So far, there are no studies about whether EMT was associated with amiodarone-induced pulmonary ...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480545.2018.1497055
更新日期:2020-07-01 00:00:00
abstract::This Visual Basic computer program has been developed for drug dosage conversions using metabolically active mass (MAM) of the animals. The two body weights (one with known dosage and the other, for which the dosage has to be calculated) and the known dosage are entered in the respective input boxes and the appropriat...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1081/dct-120017557
更新日期:2003-02-01 00:00:00
abstract::Antioxidant activity of Acacia salicina extracts was determined by the ability of each extract to inhibit lipid peroxidation, to protect against DNA strand scission induced by hydroxyl radicals, and to scavenge the free radical, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(*+)). The IC(50) values of t...
journal_title:Drug and chemical toxicology
pub_type: 杂志文章
doi:10.1080/01480540802593899
更新日期:2009-01-01 00:00:00