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Masayuki Kimura, Sayaka Mizukami, Yousuke Watanabe, Nobuhiko Onda, Toshinori Yoshida, Makoto Shibutani
The present study aimed to determine the onset time of hepatocarcinogen/hepatocarcinogenic tumor promoter-specific cell proliferation, apoptosis and aberrant cell cycle regulation after post-initiation treatment. Six-week-old rats were treated with the genotoxic hepatocarcinogen, carbadox (CRB), the marginally hepatocarcinogenic leucomalachite green (LMG), the tumor promoter, β-naphthoflavone (BNF) or the non-carcinogenic hepatotoxicant, acetaminophen, for 2, 4 or 6 weeks during the post-initiation phase using a medium-term liver bioassay...
August 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Xu Wang, María-Aránzazu Martínez, Guyue Cheng, Zhaoying Liu, Lingli Huang, Menghong Dai, Dongmei Chen, María-Rosa Martínez-Larrañaga, Arturo Anadón, Zonghui Yuan
Quinoxaline 1,4-dioxide derivatives (QdNOs) have been widely used as growth promoters and antibacterial agents. Carbadox (CBX), olaquindox (OLA), quinocetone (QCT), cyadox (CYA) and mequindox (MEQ) are the classical members of QdNOs. Some members of QdNOs are known to cause a variety of toxic effects. To date, however, almost no review has addressed the toxicity and metabolism of QdNOs in relation to oxidative stress. This review focused on the research progress associated with oxidative stress as a plausible mechanism for QdNO-induced toxicity and metabolism...
May 2016: Drug Metabolism Reviews
Qianying Liu, Jianwu Zhang, Xun Luo, Awais Ihsan, Xianglian Liu, Menghong Dai, Guyue Cheng, Haihong Hao, Xu Wang, Zonghui Yuan
Quinoxaline-di-N-oxides (QdNOs) are potential antibacterial agents with a wide range of biological properties. Quinocetone (QCT), carbadox (CBX), olaquindox (OLA), mequindox (MEQ) and cyadox (CYA) are classical QdNOs. Though the genotoxicity of parent drugs has been evaluated, the genotoxicity of their primary N → O reduced metabolites remains unclear. In the present study, a battery of four different short-term tests, mouse lymphoma assay (MLA), Ames test, chromosomal aberration assay in vitro and bone marrow erythrocyte micronucleus assay in vivo was carried out to investigate the genotoxicity of the six primary N → O reduced metabolites...
July 2016: Food and Chemical Toxicology
Tao Le, Liqian Zhu, Huan Yu
A novel and reliable dual-label direct competitive fluorescence-linked immunosorbent assay (dc-FLISA) based on quantum dots (QDs) was developed for the simultaneous determination of the major metabolites of Carbadox and Olaquindox residues in animal tissues, using anti-QCA monoclonal antibodies and anti-MQCA polyclonal antibodies labeled with QD520 and QD635, respectively. The limits of detection for QCA and MQCA were 0.05 and 0.07ng/ml, respectively. The method was used to analyze fortified samples and analyte recoveries ranged from 81...
May 15, 2016: Food Chemistry
Tao Le, Liqian Zhu, Lihui Shu, Lei Zhang
An immunochromatographic (ICG) strip was developed for the simultaneous quantitative determination of five quinoxaline-1,4-dioxides in animal feed. For this purpose, polyclonal antibodies (PcAb) with group-specific quinoxaline-1,4-dioxides were conjugated to colloidal gold particles as the detection reagent for ICG strips to test for quinoxaline-1,4-dioxides. This method achieved semi-quantitative detection of quinoxaline-1,4-dioxides within 5-10 min. The visual lower detection limits of the strip for quinocetone, cyadox, carbadox, mequindox and olaquindox were 10, 15, 15, 20 and 20 ng ml(-1), respectively...
2016: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Keita Kajiwara, Midori Kozawa, Takuya Kanazawa, Kouji Uetsuka, Hiromi Nakajima, Yoshikazu Adachi
Twenty nine isolates identified as Brachyspira hyodysenteriae were most susceptible to carbadox and metronidazole, whereas they were resistant to macrolides. The isolates showed intermediate susceptibility to tiamulin, lincomycin, penicillin G, ampicillin, chloramphenicol, tetracycline, enrofloxacin and valnemulin, with MIC50 values ranging from 0.39 to 3.13.
March 2016: Journal of Veterinary Medical Science
Masayuki Kimura, Sayaka Mizukami, Yousuke Watanabe, Yasuko Hasegawa-Baba, Nobuhiko Onda, Toshinori Yoshida, Makoto Shibutani
We aimed to clarify the hepatocarcinogen-specific disruption of cell cycle checkpoint functions and its time course after repeated administration of hepatocarcinogens. Thus, rats were repeatedly administered with hepatocarcinogens (methapyrilene, carbadox and thioacetamide), a marginal hepatocarcinogen (leucomalachite green), hepatocarcinogenic promoters (oxfendazole and β-naphthoflavone) or non-carcinogenic hepatotoxicants (promethazine and acetaminophen) for 7, 28 or 90 days, and the temporal changes in cell proliferation, expression of G1/S and spindle checkpoint-related molecules, and apoptosis were examined using immunohistochemistry and/or real-time RT-PCR analysis...
December 2015: Journal of Toxicological Sciences
Mark L Ferrey, Steven Heiskary, Richard Grace, M Coreen Hamilton, April Lueck
Water from 50 randomly selected lakes across Minnesota, USA, was analyzed for pharmaceuticals, personal care products, hormones, and other commercial or industrial chemicals in conjunction with the US Environmental Protection Agency's 2012 National Lakes Assessment. Thirty-eight of the 125 chemicals analyzed were detected at least once, all at parts per trillion concentrations. The most widely detected was N,N-diethyl-m-toluamide, present in 48% of the lakes sampled. Amitriptyline, a widely used antidepressant, was found in 28% of the lakes...
November 2015: Environmental Toxicology and Chemistry
Wagner Lutero Souza Dibai, Juarez Fabiano de Alkimin Filho, Fabiano Aurélio da Silva Oliveira, Débora Cristina Sampaio de Assis, Leonardo José Camargos Lara, Tadeu Chaves de Figueiredo, Silvana de Vasconcelos Cançado
Carbadox (CBX) and olaquindox (OLA) were used in poultry and swine feed for growth promotion, to improve feed efficiency and increase the rate of weight gain. However, the use of these agents in feedingstuffs was prohibited because of concerns about their toxicity. Regulatory laboratories are required to have suitably validated analytical methods to ensure compliance with the ban. A quantitative and confirmatory method for determining the presence of CBX and OLA in poultry and swine feed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed, optimized, and validated...
November 1, 2015: Talanta
Giulia Segato, Giancarlo Biancotto, Fabrizio Agnoletti, Giacomo Berto, Clara Montesissa, Cristiana Benetti
For the treatment of rabbit dysentery and bacterial enteritis, veterinary practitioners often adopt veterinary medicinal products authorised for other food-producing species, but in some cases non-authorised drugs frequently used in the past, such as carbadox and olaquindox, might be illegally adopted. To verify the carbadox and olaquindox distribution and persistence in rabbit tissues, two independent in vivo studies were carried out. In the first study, 24 healthy rabbits received water medicated with carbadox at 100 mg l(-1) over a period 28 days, whereas in the second one, 24 healthy rabbits were administered water containing olaquindox at 100 mg l(-1)...
2015: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Xu Wang, Huahai Zhang, Lingli Huang, Yuanhu Pan, Juan Li, Dongmei Chen, Guyue Cheng, Haihong Hao, Yanfei Tao, Zhenli Liu, Zonghui Yuan
Quinoxaline 1,4-dioxides (QdNOs) are synthetic agents with a wide range of biological activities. However, the mechanism of DNA damage mediated by QdNOs is far from clear. Five classical QdNOs, quinocetone (QCT), mequindox (MEQ), carbadox (CBX), olaquindox (OLA), and cyadox (CYA), were used to investigate the genotoxicity of QdNOs. The deoxidation rate of QdNOs was presumed to play a role in their genotoxicity. Deoxidation rates of QdNOs in both rat and pig liver microsomes were investigated using LC/MS-IT/TOF, and their relative quantification was achieved with HPLC...
March 16, 2015: Chemical Research in Toxicology
Liudmila Kulakova, Andrey Galkin, Catherine Z Chen, Noel Southall, Juan J Marugan, Wei Zheng, Osnat Herzberg
Giardiasis is a severe intestinal parasitic disease caused by Giardia lamblia, which inflicts many people in poor regions and is the most common parasitic infection in the United States. Current standard care drugs are associated with undesirable side effects, treatment failures, and an increasing incidence of drug resistance. As follow-up to a high-throughput screening of an approved drug library, which identified compounds lethal to G. lamblia trophozoites, we have determined the minimum lethal concentrations of 28 drugs and advanced 10 of them to in vivo studies in mice...
December 2014: Antimicrobial Agents and Chemotherapy
Torey Looft, Heather K Allen, Thomas A Casey, David P Alt, Thaddeus B Stanton
Antibiotics are used in livestock and poultry production to treat and prevent disease as well as to promote animal growth. Carbadox is an in-feed antibiotic that is widely used in swine production to prevent dysentery and to improve feed efficiency. The goal of this study was to characterize the effects of carbadox and its withdrawal on the swine gut microbiota. Six pigs (initially 3-weeks old) received feed containing carbadox and six received unamended feed. After 3-weeks of continuous carbadox administration, all pigs were switched to a maintenance diet without carbadox...
2014: Frontiers in Microbiology
Bradley L Bearson, Heather K Allen, Brian W Brunelle, In Soo Lee, Sherwood R Casjens, Thaddeus B Stanton
Antibiotics are used for disease therapeutic or preventative effects in humans and animals, as well as for enhanced feed conversion efficiency in livestock. Antibiotics can also cause undesirable effects in microbial populations, including selection for antibiotic resistance, enhanced pathogen invasion, and stimulation of horizontal gene transfer. Carbadox is a veterinary antibiotic used in the US during the starter phase of swine production for improved feed efficiency and control of swine dysentery and bacterial swine enteritis...
2014: Frontiers in Microbiology
Tomasz Sniegocki, Malgorzata Gbylik-Sikorska, Andrzej Posyniak, Jan Zmudzki
This paper presents LC-MS/MS method that was developed for the simultaneous determination and confirmation metabolites of carbadox (desoxycarbadox, quinoxaline-2-carboxylic) and olaquindox (3-methylquinoxaline-2-carboxylic acid) residues in pig muscle tissues at concentrations ≤3.0μgkg(-1). Pig muscle tissues were deproteinated with meta-phosphoric acid in methanol and then were extracted with ethyl acetate:dichloromethane (50:50, v/v). The whole extracts were evaporated to dryness in rotary evaporator at 45°C, and dry residues were re-dissolved in 0...
January 1, 2014: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Wenxiao Jiang, Ross C Beier, Zhanhui Wang, Yongning Wu, Jianzhong Shen
Immunoassays contribute greatly to food safety. Yet there are no reported immunoassays that simultaneously detect MQCA and QCA, the marker residues for olaquindox and carbadox, respectively. Here, a broad-specificity mAb was successfully produced, and the mAb showed good cross-reactivity with both MQCA and QCA, having IC50 values in buffer of 4.8 and 9.6 ng/mL, respectively. The calibration curves ranged from 0.3 to 81 μg/kg. The average recoveries ranged from 76% to 108% at different spiked levels (2, 4, and 8 μg/kg for MQCA; and 4, 10, and 20 μg/kg for QCA), and the intra-/interday coefficients of variation were 4...
October 23, 2013: Journal of Agricultural and Food Chemistry
Yiling Chen, Huichun Zhang
Rapid reduction of carbadox (CDX), olaquindox and several other aromatic N-oxides were investigated in aqueous solution containing Fe(II) and tiron. Consistent with previous work, the 1:2 Fe(II)-tiron complex, FeL2(6-), is the dominant reactive species as its concentration linearly correlates with the observed rate constant kobs under various conditions. The N-oxides without any side chains were much less reactive, suggesting direct reduction of the N-oxides is slow. UV-vis spectra suggest FeL2(6-) likely forms 5- or 7-membered rings with CDX and olaquindox through the N and O atoms on the side chain...
October 1, 2013: Environmental Science & Technology
Matt T Brewer, Nalee Xiong, Kristi L Anderson, Steve A Carlson
OBJECTIVE: To assess antimicrobial resistance and transfer of virulence genes facilitated by subtherapeutic concentrations of antimicrobials in swine intestines. ANIMALS: 20 anesthetized pigs experimentally inoculated with donor and recipient bacteria. PROCEDURES: 4 recipient pathogenic bacteria (Salmonella enterica serotype Typhimurium, Yersinia enterocolitica, Shigella flexneri, or Proteus mirabilis) were incubated with donor bacteria in the presence of subinhibitory concentrations of 1 of 16 antimicrobials in isolated ligated intestinal loops in swine...
August 2013: American Journal of Veterinary Research
Jiannan Yang, Zhaoying Liu, Mei Li, Xinghui Qiu
Quinoxaline derivatives (quinoxalines) comprise a class of drugs that have been widely used as animal antimicrobial agents and feed additives. Although the metabolism of quinoxaline drugs has been mostly studied using chicken liver microsomes, the biochemical mechanism of biotransformation of these chemicals in the chicken has yet to be characterized. In this study, using bacteria produced enzymes, we demonstrated that both CYP1A4 and CYP1A5 participate in the oxidative metabolism of quinoxalines. For CYP1A5, three hydroxylated metabolites of quinocetone were generated...
August 2013: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
W T Oliver, J E Wells
Lysozyme is a 1,4-β-N-acetylmuramidase that has antimicrobial properties. The objective of this experiment was to determine if lysozyme in nursery diets improved growth performance and gastrointestinal health of pigs weaned from the sow at 24 d of age. Two replicates of 96 pigs (192 total; 96 males, 96 females) were weaned from the sow at 24 d of age, blocked by BW and gender, and then assigned to 1 of 24 pens (4 pigs/pen). Each block was randomly assigned 1 of 3 dietary treatments for 28 d: control (two 14-d phases), control + antibiotics (carbadox/copper sulfate), or control + lysozyme (100 mg/kg diet)...
July 2013: Journal of Animal Science
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