Olaquindox

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Zonghui Yuan - One of the best experts on this subject based on the ideXlab platform.

  • deoxidation rates play a critical role in dna damage mediated by important synthetic drugs quinoxaline 1 4 dioxides
    Chemical Research in Toxicology, 2015
    Co-Authors: Xu Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Huahai Zhang, Yuanhu Pan, Guyue Cheng, Haihong Hao, Zonghui Yuan
    Abstract:

    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. To reveal the relationships between the deoxidation rate and genotoxicity, cell damage, oxidative stress, and DNA damage were detected. Under low oxygen conditions, the rank order of the desoxy and bidesoxy rates in rat and pig liver microsomes was QCT < CBX < MEQ < OLA < CYA and QCT < MEQ < CBX < OLA < CYA, respectively. Only desoxy-quinoxalines were detected under aerobic conditions. The concentrations of deoxidized metabolites under low o...

  • two generation reproduction and teratogenicity studies of feeding quinocetone fed to wistar rats
    Food and Chemical Toxicology, 2012
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Dongmei Chen, Dapeng Peng, Awais Ihsan, Wei Zhang, Zonghui Yuan
    Abstract:

    Abstract To investigate the reproductive toxicity and teratogenic potential of quinocetone, a growth promoting agent, Wistar rats were fed different diets containing 0, 50, 300 and 1800 mg/kg quinocetone or 300 mg/kg Olaquindox. Groups of 15 males and 30 females (F0) were fed through a 10-week prebreed period as well as during mating, gestation, parturition and lactation. At weaning, 12 males and 24 females of F1 generation weanlings per group were selected randomly as parents for F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At the highest quinocetone group, body weights in F0 and F1 rats, fetal body weight on day 21 after birth and number of viable fetuses in F0 and F1 generation significantly decreased. In teratogenicity study, groups of 12 males and 24 females were fed with the same diets through a 12-week prebreed period and matting periods. Pregnant rats were subjected to cesarean section on GD 20 for teratogenic examination. At the highest quinocetone group, body weights and feed efficiency, fetal body lengths, tail lengths, litter weights and number of viable fetuses significantly decreased. The NOAEL for reproduction/development of quinocetone for rats was estimated to be 300 mg/kg diet.

  • two generation reproduction and teratogenicity studies of feeding cyadox in wistar rats
    Food and Chemical Toxicology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Awais Ihsan, Wen Zhou, Guijie Fang, Zonghui Yuan
    Abstract:

    Abstract To investigate the teratogenic potential and reproductive toxicity of cyadox, a growth promoting agent, Wistar rats (F0) were fed with diets containing cyadox (0, 50, 150 and 2500 mg/kg) or Olaquindox (150 mg/kg), approximately equivalent to cyadox 5, 15, 250 or Olaquindox 15 mg/kg b.w./day across two generations. Half of the pregnant rats (F0, F1b) were subjected to caesarean section on gestational day 20 for teratogenic examination and the other half produced pups F1a and F2a, respectively. At the 250 mg/kg b.w./day cyadox group, body weights of F1b pregnant rats and F2a on day 21 after birth decreased; fetal body lengths and tail lengths decreased; the number of fetal resorptions increased significantly; litter weights, number of viable fetuses decreased; number of embryo resorptions increased significantly; number of liveborn F1a, F1b and F2a decreased. No macroscopic or microscopic change of any significance was found in the reproductive organs. Significant increases in the incidence of cervial ribs or lumbar ribs in F2a pups and significant increases of relative organ weight of testis and epididymis in F1b were observed at the 250 mg/kg b.w./day cyadox group. The NOAEL for reproduction/development of cyadox for rats was estimated to be 150 mg/kg diet, which was equivalent to approximately 15 mg/kg b.w./day.

  • a chronic toxicity study of cyadox in wistar rats
    Regulatory Toxicology and Pharmacology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Zhenli Liu, Awais Ihsan, Wen Zhou, Zonghui Yuan
    Abstract:

    To investigate the chronic toxicity of cyadox, a growth promoting agent, five groups of Wistar rats (30 rats/group/sex) were fed with the diets containing cyadox (0, 100, 400 and 2000 mg/kg) or Olaquindox (400 mg/kg) for 78 weeks. There were significant decreases in body weights in both genders during most of the study period in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats. Significant decreases in serum alkaline aminotransferase in the 2000 mg/kg cyadox rats at weeks 26, 52 and 78 were observed. Relative weights of liver and kidney were significantly increased in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats at weeks 26, 52 and 78. A significant increase in relative brain and heart weights in 2000 mg/kg cyadox males was observed. The histopathological examinations revealed that 2000 mg/kg cyadox diet or 400 mg/kg Olaquindox diet could induce proliferation of bile canaliculi in the portal area of liver and swelling and fatty degeneration of the proximal renal tubular epithelial cells in kidneys. In conclusion, the target organs of cyadox for rats were liver and kidney. The no-observed-adverse-effect level of cyadox in this study was estimated to be 400 mg/kg diet.

  • Residue depletion and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid after dietary administration of Olaquindox in pigs.
    Journal of Agricultural and Food Chemistry, 2010
    Co-Authors: Bo Yang, Yulian Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Yu Liu, Ke Fang, Yueping Chen, Zonghui Yuan
    Abstract:

    A residue depletion study was performed to investigate the tissue kinetics and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residue of Olaquindox (OLA), in pigs. Twenty-five pigs were randomly divided into a test and a control group. The former group was treated with 100 mg/kg OLA in its feed for 30 consecutive days, and the latter was given blank feed for the same period. One control and four treated animals were slaughtered at 0.5, 3, 10, 17, and 28 days post-medication. Muscle, liver, kidney, fat, and plasma samples were collected and analyzed using the validated high-performance liquid chromatography method (HPLC). Results showed that the tissue concentration of MQCA in the liver > kidney > fat > muscle, at almost all time points. The half-lives of MQCA in the muscle, liver, kidney, fat, and plasma were 12, 8, 15, 8, and 6 days, respectively. A withdrawal period of 38 days was calculated using the statistical method recommended by the European Medical Evaluation Agency (EMEA). Good correlations between tissue and plasma MQCA levels were found in the present study with correlation coefficients of more than 0.92. These correlations would be helpful in the routine monitoring of OLA in porcine tissues, without sacrificing the animals.

Lingli Huang - One of the best experts on this subject based on the ideXlab platform.

  • deoxidation rates play a critical role in dna damage mediated by important synthetic drugs quinoxaline 1 4 dioxides
    Chemical Research in Toxicology, 2015
    Co-Authors: Xu Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Huahai Zhang, Yuanhu Pan, Guyue Cheng, Haihong Hao, Zonghui Yuan
    Abstract:

    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. To reveal the relationships between the deoxidation rate and genotoxicity, cell damage, oxidative stress, and DNA damage were detected. Under low oxygen conditions, the rank order of the desoxy and bidesoxy rates in rat and pig liver microsomes was QCT < CBX < MEQ < OLA < CYA and QCT < MEQ < CBX < OLA < CYA, respectively. Only desoxy-quinoxalines were detected under aerobic conditions. The concentrations of deoxidized metabolites under low o...

  • Olaquindox MICs and oqxA containing in the clinical strains isolated from pigs before and after usage of growth promoters.
    2013
    Co-Authors: Wentao Guo, Yulian Wang, Lingli Huang, Dapeng Peng, Xu Wang, Haihong Hao, Menghong Dai, Hailan Wang, Min Yao, Yawei Sun
    Abstract:

    Olaquindox MICs and oqxA containing in the clinical strains isolated from pigs before and after usage of growth promoters.

  • two generation reproduction and teratogenicity studies of feeding quinocetone fed to wistar rats
    Food and Chemical Toxicology, 2012
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Dongmei Chen, Dapeng Peng, Awais Ihsan, Wei Zhang, Zonghui Yuan
    Abstract:

    Abstract To investigate the reproductive toxicity and teratogenic potential of quinocetone, a growth promoting agent, Wistar rats were fed different diets containing 0, 50, 300 and 1800 mg/kg quinocetone or 300 mg/kg Olaquindox. Groups of 15 males and 30 females (F0) were fed through a 10-week prebreed period as well as during mating, gestation, parturition and lactation. At weaning, 12 males and 24 females of F1 generation weanlings per group were selected randomly as parents for F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At the highest quinocetone group, body weights in F0 and F1 rats, fetal body weight on day 21 after birth and number of viable fetuses in F0 and F1 generation significantly decreased. In teratogenicity study, groups of 12 males and 24 females were fed with the same diets through a 12-week prebreed period and matting periods. Pregnant rats were subjected to cesarean section on GD 20 for teratogenic examination. At the highest quinocetone group, body weights and feed efficiency, fetal body lengths, tail lengths, litter weights and number of viable fetuses significantly decreased. The NOAEL for reproduction/development of quinocetone for rats was estimated to be 300 mg/kg diet.

  • two generation reproduction and teratogenicity studies of feeding cyadox in wistar rats
    Food and Chemical Toxicology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Awais Ihsan, Wen Zhou, Guijie Fang, Zonghui Yuan
    Abstract:

    Abstract To investigate the teratogenic potential and reproductive toxicity of cyadox, a growth promoting agent, Wistar rats (F0) were fed with diets containing cyadox (0, 50, 150 and 2500 mg/kg) or Olaquindox (150 mg/kg), approximately equivalent to cyadox 5, 15, 250 or Olaquindox 15 mg/kg b.w./day across two generations. Half of the pregnant rats (F0, F1b) were subjected to caesarean section on gestational day 20 for teratogenic examination and the other half produced pups F1a and F2a, respectively. At the 250 mg/kg b.w./day cyadox group, body weights of F1b pregnant rats and F2a on day 21 after birth decreased; fetal body lengths and tail lengths decreased; the number of fetal resorptions increased significantly; litter weights, number of viable fetuses decreased; number of embryo resorptions increased significantly; number of liveborn F1a, F1b and F2a decreased. No macroscopic or microscopic change of any significance was found in the reproductive organs. Significant increases in the incidence of cervial ribs or lumbar ribs in F2a pups and significant increases of relative organ weight of testis and epididymis in F1b were observed at the 250 mg/kg b.w./day cyadox group. The NOAEL for reproduction/development of cyadox for rats was estimated to be 150 mg/kg diet, which was equivalent to approximately 15 mg/kg b.w./day.

  • a chronic toxicity study of cyadox in wistar rats
    Regulatory Toxicology and Pharmacology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Zhenli Liu, Awais Ihsan, Wen Zhou, Zonghui Yuan
    Abstract:

    To investigate the chronic toxicity of cyadox, a growth promoting agent, five groups of Wistar rats (30 rats/group/sex) were fed with the diets containing cyadox (0, 100, 400 and 2000 mg/kg) or Olaquindox (400 mg/kg) for 78 weeks. There were significant decreases in body weights in both genders during most of the study period in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats. Significant decreases in serum alkaline aminotransferase in the 2000 mg/kg cyadox rats at weeks 26, 52 and 78 were observed. Relative weights of liver and kidney were significantly increased in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats at weeks 26, 52 and 78. A significant increase in relative brain and heart weights in 2000 mg/kg cyadox males was observed. The histopathological examinations revealed that 2000 mg/kg cyadox diet or 400 mg/kg Olaquindox diet could induce proliferation of bile canaliculi in the portal area of liver and swelling and fatty degeneration of the proximal renal tubular epithelial cells in kidneys. In conclusion, the target organs of cyadox for rats were liver and kidney. The no-observed-adverse-effect level of cyadox in this study was estimated to be 400 mg/kg diet.

Dongmei Chen - One of the best experts on this subject based on the ideXlab platform.

  • deoxidation rates play a critical role in dna damage mediated by important synthetic drugs quinoxaline 1 4 dioxides
    Chemical Research in Toxicology, 2015
    Co-Authors: Xu Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Huahai Zhang, Yuanhu Pan, Guyue Cheng, Haihong Hao, Zonghui Yuan
    Abstract:

    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. To reveal the relationships between the deoxidation rate and genotoxicity, cell damage, oxidative stress, and DNA damage were detected. Under low oxygen conditions, the rank order of the desoxy and bidesoxy rates in rat and pig liver microsomes was QCT < CBX < MEQ < OLA < CYA and QCT < MEQ < CBX < OLA < CYA, respectively. Only desoxy-quinoxalines were detected under aerobic conditions. The concentrations of deoxidized metabolites under low o...

  • two generation reproduction and teratogenicity studies of feeding quinocetone fed to wistar rats
    Food and Chemical Toxicology, 2012
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Dongmei Chen, Dapeng Peng, Awais Ihsan, Wei Zhang, Zonghui Yuan
    Abstract:

    Abstract To investigate the reproductive toxicity and teratogenic potential of quinocetone, a growth promoting agent, Wistar rats were fed different diets containing 0, 50, 300 and 1800 mg/kg quinocetone or 300 mg/kg Olaquindox. Groups of 15 males and 30 females (F0) were fed through a 10-week prebreed period as well as during mating, gestation, parturition and lactation. At weaning, 12 males and 24 females of F1 generation weanlings per group were selected randomly as parents for F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At the highest quinocetone group, body weights in F0 and F1 rats, fetal body weight on day 21 after birth and number of viable fetuses in F0 and F1 generation significantly decreased. In teratogenicity study, groups of 12 males and 24 females were fed with the same diets through a 12-week prebreed period and matting periods. Pregnant rats were subjected to cesarean section on GD 20 for teratogenic examination. At the highest quinocetone group, body weights and feed efficiency, fetal body lengths, tail lengths, litter weights and number of viable fetuses significantly decreased. The NOAEL for reproduction/development of quinocetone for rats was estimated to be 300 mg/kg diet.

  • Residue depletion and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid after dietary administration of Olaquindox in pigs.
    Journal of Agricultural and Food Chemistry, 2010
    Co-Authors: Bo Yang, Yulian Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Yu Liu, Ke Fang, Yueping Chen, Zonghui Yuan
    Abstract:

    A residue depletion study was performed to investigate the tissue kinetics and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residue of Olaquindox (OLA), in pigs. Twenty-five pigs were randomly divided into a test and a control group. The former group was treated with 100 mg/kg OLA in its feed for 30 consecutive days, and the latter was given blank feed for the same period. One control and four treated animals were slaughtered at 0.5, 3, 10, 17, and 28 days post-medication. Muscle, liver, kidney, fat, and plasma samples were collected and analyzed using the validated high-performance liquid chromatography method (HPLC). Results showed that the tissue concentration of MQCA in the liver > kidney > fat > muscle, at almost all time points. The half-lives of MQCA in the muscle, liver, kidney, fat, and plasma were 12, 8, 15, 8, and 6 days, respectively. A withdrawal period of 38 days was calculated using the statistical method recommended by the European Medical Evaluation Agency (EMEA). Good correlations between tissue and plasma MQCA levels were found in the present study with correlation coefficients of more than 0.92. These correlations would be helpful in the routine monitoring of OLA in porcine tissues, without sacrificing the animals.

  • metabolism of Olaquindox in rat liver microsomes structural elucidation of metabolites by high performance liquid chromatography combined with ion trap time of flight mass spectrometry
    Rapid Communications in Mass Spectrometry, 2008
    Co-Authors: Zhaoying Liu, Yulian Wang, Lingli Huang, Dongmei Chen, Yanfei Tao, Menghong Dai, Zonghui Yuan
    Abstract:

    Olaquindox (N-(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamide-1,4-dioxide) is a growth-promoting feed additive for food-producing animals. Its toxicity is closely related to the metabolism. The complete metabolic pathways of Olaquindox are not revealed. To improve studies of the metabolism and toxicity of Olaquindox, its biotransformation in rat liver microsomes and the structure of its metabolites using high-performance liquid chromatography combined with ion trap/time-of-flight mass spectrometry (LC/MS-ITTOF) were investigated. When Olaquindox was incubated with an NADPH-generating system and rat liver microsomes, ten metabolites (M1-M10) were detected. The structures of these metabolites were identified from mass spectra and comparison of their changes in their accurate molecular masses and fragment ions with those of the parent drug. With the high resolution and good mass accuracy achieved by this technique, the elemental compositions of the metabolites and their fragment ions were exactly determined. The results indicate that the N --> O group reduction is the main metabolic pathway of Olaquindox metabolism in rat liver microsomes, because abundant 1-desOlaquindox (M2), 4-desOlaquindox (M1) and bisdesoxyOlaquindox (M9) were produced during the incubation step. Seven other minor metabolites were revealed which were considered to be hydroxylation metabolites, based on the position of the quinoxaline ring or 3-methyl group and a carboxylic acid derivative on the side chain at position 2 of the quinoxaline ring. Among the identified metabolites, five new hydroxylated metabolites (M3-M7) were found for the first time in rat liver microsomes. This work will conduce to complete clarification of Olaquindox metabolism, and improve the in vivo metabolism of Olaquindox in food animals.

  • development of a high performance liquid chromatography method for the simultaneous quantification of quinoxaline 2 carboxylic acid and methyl 3 quinoxaline 2 carboxylic acid in animal tissues
    Journal of Chromatography A, 2007
    Co-Authors: Yujie Wu, Huan Yu, Yulian Wang, Lingli Huang, Dongmei Chen, Dapeng Peng, Zonghui Yuan
    Abstract:

    Abstract A method of high-performance liquid chromatography with UV detection has been established for simultaneous quantitative determination of quinoxaline-2-carboxylic acid (QCA) and methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residues for carbadox (CBX) and Olaquindox (OLA), respectively, in the muscles and livers of porcine and chicken and in the muscle of fish. Tissue samples were subject to acid hydrolysis followed by liquid–liquid extraction and Oasis MAX solid-phase extraction clean-up. The method was validated according to the EU Commission Decision 2002/657/EC. The decision limits (CCα) were 0.7–2.6 μg/kg and the detection capabilities (CCβ) were 1.3–5.6 μg/kg for QCA and MQCA in tissues. The recoveries of QCA and MQCA, spiked at levels of 2–100 μg/kg, were from 70 to 110%; the relative standard deviation values were

Yulian Wang - One of the best experts on this subject based on the ideXlab platform.

  • Olaquindox MICs and oqxA containing in the clinical strains isolated from pigs before and after usage of growth promoters.
    2013
    Co-Authors: Wentao Guo, Yulian Wang, Lingli Huang, Dapeng Peng, Xu Wang, Haihong Hao, Menghong Dai, Hailan Wang, Min Yao, Yawei Sun
    Abstract:

    Olaquindox MICs and oqxA containing in the clinical strains isolated from pigs before and after usage of growth promoters.

  • two generation reproduction and teratogenicity studies of feeding quinocetone fed to wistar rats
    Food and Chemical Toxicology, 2012
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Dongmei Chen, Dapeng Peng, Awais Ihsan, Wei Zhang, Zonghui Yuan
    Abstract:

    Abstract To investigate the reproductive toxicity and teratogenic potential of quinocetone, a growth promoting agent, Wistar rats were fed different diets containing 0, 50, 300 and 1800 mg/kg quinocetone or 300 mg/kg Olaquindox. Groups of 15 males and 30 females (F0) were fed through a 10-week prebreed period as well as during mating, gestation, parturition and lactation. At weaning, 12 males and 24 females of F1 generation weanlings per group were selected randomly as parents for F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At the highest quinocetone group, body weights in F0 and F1 rats, fetal body weight on day 21 after birth and number of viable fetuses in F0 and F1 generation significantly decreased. In teratogenicity study, groups of 12 males and 24 females were fed with the same diets through a 12-week prebreed period and matting periods. Pregnant rats were subjected to cesarean section on GD 20 for teratogenic examination. At the highest quinocetone group, body weights and feed efficiency, fetal body lengths, tail lengths, litter weights and number of viable fetuses significantly decreased. The NOAEL for reproduction/development of quinocetone for rats was estimated to be 300 mg/kg diet.

  • two generation reproduction and teratogenicity studies of feeding cyadox in wistar rats
    Food and Chemical Toxicology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Awais Ihsan, Wen Zhou, Guijie Fang, Zonghui Yuan
    Abstract:

    Abstract To investigate the teratogenic potential and reproductive toxicity of cyadox, a growth promoting agent, Wistar rats (F0) were fed with diets containing cyadox (0, 50, 150 and 2500 mg/kg) or Olaquindox (150 mg/kg), approximately equivalent to cyadox 5, 15, 250 or Olaquindox 15 mg/kg b.w./day across two generations. Half of the pregnant rats (F0, F1b) were subjected to caesarean section on gestational day 20 for teratogenic examination and the other half produced pups F1a and F2a, respectively. At the 250 mg/kg b.w./day cyadox group, body weights of F1b pregnant rats and F2a on day 21 after birth decreased; fetal body lengths and tail lengths decreased; the number of fetal resorptions increased significantly; litter weights, number of viable fetuses decreased; number of embryo resorptions increased significantly; number of liveborn F1a, F1b and F2a decreased. No macroscopic or microscopic change of any significance was found in the reproductive organs. Significant increases in the incidence of cervial ribs or lumbar ribs in F2a pups and significant increases of relative organ weight of testis and epididymis in F1b were observed at the 250 mg/kg b.w./day cyadox group. The NOAEL for reproduction/development of cyadox for rats was estimated to be 150 mg/kg diet, which was equivalent to approximately 15 mg/kg b.w./day.

  • a chronic toxicity study of cyadox in wistar rats
    Regulatory Toxicology and Pharmacology, 2011
    Co-Authors: Xu Wang, Yulian Wang, Lingli Huang, Zhenli Liu, Awais Ihsan, Wen Zhou, Zonghui Yuan
    Abstract:

    To investigate the chronic toxicity of cyadox, a growth promoting agent, five groups of Wistar rats (30 rats/group/sex) were fed with the diets containing cyadox (0, 100, 400 and 2000 mg/kg) or Olaquindox (400 mg/kg) for 78 weeks. There were significant decreases in body weights in both genders during most of the study period in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats. Significant decreases in serum alkaline aminotransferase in the 2000 mg/kg cyadox rats at weeks 26, 52 and 78 were observed. Relative weights of liver and kidney were significantly increased in 2000 mg/kg cyadox and 400 mg/kg Olaquindox rats at weeks 26, 52 and 78. A significant increase in relative brain and heart weights in 2000 mg/kg cyadox males was observed. The histopathological examinations revealed that 2000 mg/kg cyadox diet or 400 mg/kg Olaquindox diet could induce proliferation of bile canaliculi in the portal area of liver and swelling and fatty degeneration of the proximal renal tubular epithelial cells in kidneys. In conclusion, the target organs of cyadox for rats were liver and kidney. The no-observed-adverse-effect level of cyadox in this study was estimated to be 400 mg/kg diet.

  • Residue depletion and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid after dietary administration of Olaquindox in pigs.
    Journal of Agricultural and Food Chemistry, 2010
    Co-Authors: Bo Yang, Yulian Wang, Lingli Huang, Dongmei Chen, Zhenli Liu, Yanfei Tao, Yu Liu, Ke Fang, Yueping Chen, Zonghui Yuan
    Abstract:

    A residue depletion study was performed to investigate the tissue kinetics and tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid (MQCA), the marker residue of Olaquindox (OLA), in pigs. Twenty-five pigs were randomly divided into a test and a control group. The former group was treated with 100 mg/kg OLA in its feed for 30 consecutive days, and the latter was given blank feed for the same period. One control and four treated animals were slaughtered at 0.5, 3, 10, 17, and 28 days post-medication. Muscle, liver, kidney, fat, and plasma samples were collected and analyzed using the validated high-performance liquid chromatography method (HPLC). Results showed that the tissue concentration of MQCA in the liver > kidney > fat > muscle, at almost all time points. The half-lives of MQCA in the muscle, liver, kidney, fat, and plasma were 12, 8, 15, 8, and 6 days, respectively. A withdrawal period of 38 days was calculated using the statistical method recommended by the European Medical Evaluation Agency (EMEA). Good correlations between tissue and plasma MQCA levels were found in the present study with correlation coefficients of more than 0.92. These correlations would be helpful in the routine monitoring of OLA in porcine tissues, without sacrificing the animals.

Guangming Mei - One of the best experts on this subject based on the ideXlab platform.

  • determination of marker residue of Olaquindox in fish tissue by ultra performance liquid chromatography tandem mass spectrometry
    IEEE Journal of Solid-state Circuits, 2011
    Co-Authors: Xiaojun Zhang, Hong Zhang, Bin Zheng, Xuechang Chen, Guangming Mei
    Abstract:

    Methyl-3-quinoxaline-2-carboxylic acid (MQCA) is the last major remaining detectable metabolite of Olaquindox in animal tissue. A rapid, sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the detection and quantification of MQCA in fish tissue using deuterated quinoxaline-2-carboxylic acid (d(4)-QCA) as internal standard. Various parameters affecting sample preparation, LC separation and MS/MS detection were investigated, and the optimal conditions concerned were determined. Fish tissue samples were subject to hydrochloric acid hydrolysis followed by Oasis MAX solid-phase extraction clean-up; analysis was performed using UPLC coupled to electrospray MS/MS. The chromatographic separation was achieved in less than 5 min. The limit of detection and the limit of quantification were 0.1 and 0.25 ng/g, respectively. The average recoveries of MQCA, spiked at levels of 0.25-50.0 ng/g, were from 92.7 to 104.3%. The relative standard deviation values were <6%. The validated method was successfully applied to analyze 60 batch samples collected from the local market.