Abstract:
:Garenoxacin is a des-F(6)-quinolone with a broad antibacterial spectrum, which has previously been shown to exhibit low chondrotoxicity in juvenile dogs compared with several other quinolones. A study was performed to determine whether the low chondrotoxicity observed in immature rats following garenoxacin treatment could be explained by poor penetration into cartilage tissue. Garenoxacin was orally administered to immature (4- to 5-week-old) Wistar rats as a single dose-or as doses given on 5 consecutive days-of 0 (vehicle), 200, 400, and 600 mg/kg ( n=5 per dose level). Additional groups of rats were orally dosed with 600 mg/kg ofloxacin and ciprofloxacin. One knee joint of each animal (24 h after the last dose) was studied histologically after staining with Toluidine blue. The pharmacokinetics of garenoxacin in plasma (200, 400, and 600 mg/kg) and in knee joint cartilage (200 and 600 mg/kg) was assessed in separate groups of rats ( n=55 per dose level). Concentrations of garenoxacin in plasma and cartilage were measured using an HPLC method. No signs of chondrotoxicity were observed in the immature rats treated with garenoxacin or ciprofloxacin for 5 days at the doses investigated in this study. However, ofloxacin was found to induce cartilage lesions that were typical of those seen for this quinolone. Systemic exposure to garenoxacin increased as a function of dose. Across dose and study day, mean garenoxacin plasma maximum concentration ( C(max)) and area under the concentration-time curve (AUC(tau)) values were in the range 12-26 mg/l and 33-133 mgxh/l, respectively. Garenoxacin C(max) and AUC were similar on days 1 and 5, within each dose, indicating the absence of accumulation or reduction in the systemic exposure. Values determined for T(max) (0.25-1.0 h) and T(1/2) (3.8-6.4 h) of garenoxacin in plasma did not vary with dose or study day. Although peak garenoxacin concentrations in cartilage were between equal levels to and 2.5-fold of those found in plasma, the observed ratios were somewhat lower than those reported for other quinolones, e.g. ofloxacin or sparfloxacin. Since garenoxacin appeared to be well absorbed following oral administration and concentrations in cartilage tended to be higher than those in plasma, it is unlikely that the low chondrotoxicity in comparison with other quinolones is explained by differences in the pharmacokinetics of these compounds.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Kastner M,Rahm U,Baumann-Wilschke I,Bello A,Stahlmann Rdoi
10.1007/s00204-003-0514-3keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
61-7issue
2eissn
0340-5761issn
1432-0738journal_volume
78pub_type
杂志文章abstract::The effect of duration of employment at a North American cadmium smelter on urinary metallothionein (MT), total protein, beta 2-microglobulin (beta 2-MG), glucose, cadmium, copper and zinc of 53 men was studied. The levels of all urinary parameters increased with the duration of employment. Smoking history did not aff...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00295090
更新日期:1987-02-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is known to influence vitamin A homeostasis. In order to investigate the mechanism behind this retinoid disruption, male Sprague-Dawley rats were exposed to TCDD at doses ranging from 0.1 to 100 micro g/kg body weight, and were killed 3 days after exposure. Additional groups...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-003-0457-8
更新日期:2003-07-01 00:00:00
abstract::Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent chan...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050638
更新日期:1999-11-01 00:00:00
abstract::Etoposide (ETP) and anthracyclines are applied for wide anti-cancer treatments. However, the ETP-induced cardiotoxicity remains to be a major safety issue and the underlying cardiotoxic mechanisms are not well understood. This study is aiming to unravel the cardiotoxicity profile of ETP in comparison to anthracyclines...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-018-2170-7
更新日期:2018-04-01 00:00:00
abstract::Sunitinib (SNT) is a multi-targeted receptor tyrosine kinase inhibitor that has been approved by the FDA for cancer therapy. However, its cardiotoxicity has limited the clinical applicability with no effective therapeutic approach available. As a broadband kinase inhibitor, the function of several kinases that are ess...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02448-z
更新日期:2019-06-01 00:00:00
abstract::The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerabl...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02470-1
更新日期:2019-07-01 00:00:00
abstract::Oxime-type acetylcholinesterase reactivators (oxime-AChER) are used as an adjunct in the treatment for organophosphorus anticholinesterase poisoning. Because of the widespread usage and exposure of organophosphorus compounds (OPCs), its poisoning and fatalities is obvious in pregnant women, embryos and fetuses. OPCs i...
journal_title:Archives of toxicology
pub_type: 杂志文章,评审
doi:10.1007/s00204-013-1160-z
更新日期:2014-03-01 00:00:00
abstract::Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic dr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02454-1
更新日期:2019-06-01 00:00:00
abstract::Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta-oxidation and cytochrome P450IVA1 activities. The latter induction of cytochro...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF02034935
更新日期:1991-01-01 00:00:00
abstract::Platinum coordination complexes (PtCx) are potent against several types of cancer but are often nephrotoxic. With a view to developing a PtCx nephrotoxicity model, the toxicity of cisplatin (cDDP), transplatin (tDDP) and carboplatin (CBDCA) was studied in primary cultures of rabbit proximal tubule (RPT) cells and in t...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01973705
更新日期:1993-01-01 00:00:00
abstract::Metabolism of carbaryl by rat liver and skin post-mitochondrial fraction has been measured in the presence and absence of cofactors to promote different metabolic pathways. The metabolic capacity was compared with the metabolism of carbaryl during percutaneous absorption in a static skin diffusion system using a varie...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01973722
更新日期:1991-01-01 00:00:00
abstract::The goal of the present study was to obtain an in vivo relevant prioritization method for the endocrine potencies of different polycarbonate monomers, by combining in vitro bioassay data with physiologically based kinetic (PBK) modelling. PBK models were developed for a selection of monomers, including bisphenol A (BP...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-019-02479-6
更新日期:2019-07-01 00:00:00
abstract::The first withdrawal of certain polybrominated diphenyl ethers flame retardants from the US market occurred in 2004. Since then, use of brominated non-PBDE compounds such as bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) in commercial formulations has incr...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-015-1489-6
更新日期:2016-03-01 00:00:00
abstract::The genotoxicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS) to V79 Chinese hamster cells was investigated using the induction of gene mutations, micronuclei and DNA repair synthesis as biological endpoints. CS efficiently induced micronuclei and mutants resistant to 6-thioguanine in these cells, but ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00278645
更新日期:1989-01-01 00:00:00
abstract::Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously o...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-007-0192-7
更新日期:2007-09-01 00:00:00
abstract::A pharmacokinetic profile of [14C] leptophos was determined in laying hens following a single oral dose of 400 mg/kg (0.58 muCi). Most of the radioactivity was excreted into the urine and feces. After 15 days, the total radioactivity recovered in the combined urinary-fecal excretion was 73.5% of the administered dose....
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00351968
更新日期:1976-10-28 00:00:00
abstract::Organophosphate-induced delayed polyneuropathy (OPIDP) is initiated by inhibition/aging of more than 70-75% of neuropathy target esterase (NTE). Di-n-butyl-2,2-dichlorovinyl phosphate (DBDCVP) (1 mg/kg s.c.) inhibited 96%, 86% and 83% of NTE in brain, spinal cord and peripheral nerve, respectively, and induced a typic...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00316450
更新日期:1989-01-01 00:00:00
abstract::The effects of equimolar doses of the triphenylethylene antiestrogens tamoxifen and toremifene on female Sprague-Dawley rat liver were studied in a 52-week toxicity study which included a 13-week recovery period. Liver tumors were found in four out of five rats at the highest dose level of tamoxifen (45 mg/kg per day)...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF02072035
更新日期:1993-01-01 00:00:00
abstract::The role of the functional substituents on the pyridinium ring of bisquaternary pyridinium compounds, mostly oximes, in exerting reversible and irreversible inhibition of binding of [3H]-N-methyl-4-piperidyl benzilate [( 3H]-4NMPB) to rat brain stem muscarinic receptors was studied. The drugs tested, i.e. HGG-42, HGG-...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00292614
更新日期:1985-10-01 00:00:00
abstract::Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The pre...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-017-1998-6
更新日期:2017-09-01 00:00:00
abstract::Phenobarbital pretreatment (50 mg/kg/day for 3 days orally) of male Wistar rats increased Vmax of benzene in vitro hepatic microsomal biotransformation about 6-fold without changing Km. However, benzene blood levels after oral, intraperitoneal, or subcutaneous benzene administration (3-3.5 mmoles/kg) were not influenc...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00293567
更新日期:1976-06-08 00:00:00
abstract::Since teratogenicity testing in mammals is a particular challenge from an animal welfare perspective, there is a great need for the development of alternative test systems. In this context, the zebrafish (Danio rerio) embryo has received increasing attention as a non-protected embryonic vertebrate in vivo model. The p...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-020-02928-7
更新日期:2020-10-27 00:00:00
abstract::The hepatotoxicity of acetaminophen (APAP) overdose depends on metabolic activation to a toxic reactive metabolite via hepatic mixed function oxidase. In vitro studies have indicated that APAP may also be cooxidized by prostaglandin H synthetase. The present experiments were designed to assess the possible contributio...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF01972990
更新日期:1990-01-01 00:00:00
abstract::A compound was isolated from the urine of workers exposed to carbon disulfide during the production of rayon. The compound was identified as 2-thiothiazolidine-4-carboxylic acid (TTCA) by GC/MS and NMR. A HPLC method for the quantitative determination of TTCA was elaborated and applied to urine samples. The method all...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF00297130
更新日期:1981-03-01 00:00:00
abstract::The effect of methantheline, a quaternary ammonium compound, on the reactivation by HI 6 of soman-inhibited human erythrocyte acetylcholinesterase (AChE) was investigated in vitro using purified human erythrocyte AChE or washed human erythrocytes. Methantheline itself was found to be a mixed competitive/non-competitiv...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050243
更新日期:1995-01-01 00:00:00
abstract::Phytoestrogens have been described as weak estrogens, selective estrogen receptor mediators (SERMs) or to exhibit antiestrogenic properties. However, information about their activity in combination with xenoestrogens and 17beta-estradiol in vivo, is limited. Therefore, the combinatory activity of the phytoestrogen gen...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-006-0102-4
更新日期:2006-12-01 00:00:00
abstract::Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 micrograms Ni/rat) was about 32 h in both the IT instillation ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s002040050112
更新日期:1994-01-01 00:00:00
abstract::Neuropathy Target Esterase (NTE) was initially identified as the primary target esterase of some organophosphorus compounds that cause delayed neuropathy. Some studies in vivo suggest that this protein may also perform a function in embryonic development and therefore also in cell differentiation. The aim of this work...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-010-0518-8
更新日期:2010-06-01 00:00:00
abstract::A recent intervention study demonstrated the occurrence of irilone as second most abundant isoflavone next to daidzein in human plasma after consumption of a red clover-based dietary supplement (RCDS) containing predominately formononetin ≫ biochanin A > irilone (12 % of these isoflavones). To elucidate the relevance ...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/s00204-013-1114-5
更新日期:2014-02-01 00:00:00
abstract::Liver microsomes were prepared from Wistar rat by the Ca2+ aggregation method. Under various conditions, ethyl mercury chloride (EtHgCl) or methyl mercury chloride (MeHgCl) was incubated with the microsomal preparations. After the incubation, the amounts of inorganic Hg and hydroxyl radical (.OH) in the preparations w...
journal_title:Archives of toxicology
pub_type: 杂志文章
doi:10.1007/BF02035129
更新日期:1992-01-01 00:00:00