149 results on '"Mizukawa, H."'
Search Results
2. Human Health Risk from Consumption of Marine Fish Contaminated with DDT and Its Metabolites in Maputo Bay, Mozambique
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Thompson, L. A., Ikenaka, Y., Yohannes, Y. B., Ichise, T., Ito, G., Bortey-Sam, N., van Vuren, J. J., Wepener, V., Smit, N. J., Darwish, W. S., Nakayama, S. M. M., Mizukawa, H., and Ishizuka, M.
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- 2018
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3. Biotransport of metallic trace elements from marine to terrestrial ecosystems by seabirds
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Shoji, A., Elliott, K. H., Aris-Brosou, S., Mizukawa, H., Nakayama, S. M. M., Ikenaka, Y., Ishizuka, M., Kuwae, T., Watanabe, K., Escoruela Gonzalez, J., and Watanuki, Yutaka
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Rhinoceros auklet ,Machine learning ,Mercury ,Biological transport ,Bioaccumulation - Abstract
Physical systems, such as currents and winds, have traditionally been considered responsible for transporting contaminants. Although evidence is mounting that animals play a role in this process through their movements, we still know little about how such contaminant biotransport occurs and the extent of effects at deposition sites. In the present study, we address this question by studying how rhinoceros auklets (Cerorhinca monocerata), a seabird that occurs in immense colonies (∼300 000 pairs at our study site, Teuri Island), affect contaminant levels at their colony and at nearby sites. More specifically, we hypothesize that contaminants are transported and deposited by seabirds at their colony and that these contaminants are passed on locally to the terrestrial ecosystem. To test this hypothesis, we analyzed the concentration of 9 heavy metal and metalloids, as well as δ13C and δ15N stable isotopes, in bird tissues, plants, and soil, both within and outside of the colony. The results show that rhinoceros auklets transport marine‐derived mercury (Hg), possibly from their wintering location, and deposit Hg via their feces at their breeding site, thereby contaminating plants and soils within the breeding colony. The present study confirms not only that animals can transport contaminants from marine to terrestrial ecosystems, potentially over unexpectedly long distances, but also that bird tissues contribute locally to plant contamination.
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- 2019
4. Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species
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WATANABE, K. P., KAWAI, Y. K., NAKAYAMA, S. M. M., IKENAKA, Y., MIZUKAWA, H., TAKAESU, N., ITO, M., IKUSHIRO, S.-I., SAKAKI, T., and ISHIZUKA, M.
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- 2015
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5. A glycomics approach to discover novel renal biomarkers in birds by administration of cisplatin and diclofenac to chickens
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Ishii, C., Ikenaka, Y., Ichii, O., Nakayama, S. M. M., Nishimura, S.- I., Ohashi, T., Tanaka, M., Mizukawa, H., and Ishizuka, M.
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glycan ,bird ,acute tubular necrosis ,renal biomarker ,acute interstitial nephritis - Abstract
Avian species have a unique renal structure and abundant blood flow into the kidneys. Although many birds die due to nephrotoxicity caused by chemicals, there are no early biomarkers for renal lesions. Uric acid level in blood, which is generally used as a renal biomarker, is altered when the kidney function is damaged by over 70%. Therefore, early biomarkers for kidney injury in birds are needed. In humans, glycomics has been at the forefront of biological and medical sciences, and glycans are used as biomarkers of diseases, such as carcinoma. In this study, a glycomics approach was used to screen for renal biomarkers in chicken. First, a chicken model of kidney damage was generated by injection of diclofenac or cisplatin, which cause acute interstitial nephritis (AIN) and acute tubular necrosis (ATN), respectively. The nephrotoxicity levels were determined by a blood chemical test and histopathological analysis. The plasma N-glycans were then analyzed to discover renal biomarkers in birds. Levels of 14 glycans increased between pre- and post administration in kidney-damaged chickens in the diclofenac group, and some of these glycans had the same presumptive composition as those in human renal carcinoma patients. Glycan levels did not change remarkably in the cisplatin group. It is possible that there are changes in glycan expression due to AIN, but they do not reflect ATN. Although further research is needed in other species of birds, glycans are potentially useful biomarkers for AIN in avian species.
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- 2018
6. Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease
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Nakamura, R., Yabuki, A., Ichii, O., Mizukawa, H., Yokoyama, N., and Yamato, O.
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- 2018
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7. First report on OH-PAHs in South African Clarias gariepinus bile from an urban impacted system
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Pheiffer, W, Bortey-Sam, N, Ikenaka, Y, Nakayama, SMM, Mizukawa, H, Ishizuka, M, Smit, NJ, and Pieters, R
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Freshwater toxicology, Klip River, sharptooth catfish, Soweto - Abstract
The concentrations of selected hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were determined in the bile of the African sharptooth catfish Clarias gariepinus from impoundments in the urban impacted Klip River system in Soweto, South Africa. Fish were sampled from three impoundments (Lenasia, Fleurhof, and Orlando dams) during the early high-flow season (September/October) of 2013. Biliary OH-PAHs were analysed using a high-pressure liquid chromatograph coupled to a tandem mass spectrometer (HPLC-MS/MS). Seven of the thirteen targeted metabolites were present in the fish of Soweto. The ΣOH-PAHs ranged between 0.1 and 1 876 ng ml−1, with greatest ΣOH-PAH mean at Orlando (947 ng ml−1) followed by Fleurhof (371 ng ml−1). The most dominant metabolite in the sampling area was 2–,3–OH fluorene, ranging between not detected and 1 429 ng ml−1, with the greatest mean at Orlando (709 ng ml−1). PAH metabolites quantified in C. gariepinus most likely originated from the sediments. The hepatosomatic index of the C. gariepinus increased proportionally with the biliary OH-PAH concentrations. To the authors’ knowledge this data on biliary OH-PAH for fish is the first for South Africa.Keywords: Freshwater toxicology, Klip River, sharptooth catfish, Soweto
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- 2018
8. Biotransport of metallic trace elements from marine to terrestrial ecosystems by seabirds
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Shoji, A., primary, Elliott, K.H., additional, Aris‐Brosou, S., additional, Mizukawa, H., additional, Nakayama, S.M.M., additional, Ikenaka, Y., additional, Ishizuka, M., additional, Kuwae, T., additional, Watanabe, K., additional, Escoruela Gonzalez, J., additional, and Watanuki, Y., additional
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- 2018
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9. First report on OH-PAHs in South AfricanClarias gariepinusbile from an urban impacted system
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Pheiffer, W, primary, Bortey-Sam, N, additional, Ikenaka, Y, additional, Nakayama, SMM, additional, Mizukawa, H, additional, Ishizuka, M, additional, Smit, NJ, additional, and Pieters, R, additional
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- 2018
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10. Concentrations and human health risk assessment of DDT and its metabolites in free-range and commercial chicken products from KwaZulu-Natal, South Africa
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Thompson, L. A., primary, Ikenaka, Y., additional, Yohannes, Y. B., additional, van Vuren, J. J., additional, Wepener, V., additional, Smit, N. J., additional, Darwish, W. S., additional, Nakayama, S. M. M., additional, Mizukawa, H., additional, and Ishizuka, M., additional
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- 2017
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11. Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam
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Nakayama, S. M. M., primary, Ikenaka, Y., additional, Hayami, A., additional, Mizukawa, H., additional, Darwish, W. S., additional, Watanabe, K. P., additional, Kawai, Y. K., additional, and Ishizuka, M., additional
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- 2016
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12. Recherches et mesures pour limiter l'infiltration des eaux pluviales dans un réseau séparatif pendant l'événement pluvieux
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Tanimizu, K., Tanokura, M., Nishimura, H., Miyahara, S., Mizukawa, H., Matsushima, O., Inconnu, and Brelot, Elodie
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Strategy, Water infiltration during rainfall ,separate sewage system ,Stratégie ,[SDE.IE]Environmental Sciences/Environmental Engineering - Abstract
Colloque avec actes et comité de lecture. internationale.; International audience; There have been many reports on the rapid increase in water flows into pumping stations and wastewater treatment plants during rainfall (known as “water infiltration during rainfall”) at wastewater facilities on a separate sewer system. Increased water infiltration during rainfall can overload the capacity of the facility, leading to flooding of nearby land from sewer pipelines and water damage to pumping stations and treatment plants, while also compromising the treatment capacity of treatment plants. In the current difficult economic climate, local governments in charge of the sewer system are struggling with maintenance costs associated with water infiltration during rainfall and are not able to develop adequate countermeasures. This study proposes a systematic response to the problem of water infiltration during rainfall, including survey techniques for identifying the causes and planning strategies for developing solutions. A flowrate survey procedure for assessing the impact of countermeasures to reduce water infiltration is also presented, together with examples of use. Cost-benefit analysis of countermeasures is described, together with associated case studies, and is demonstrated to be a useful technique for project evaluation.
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- 2010
13. Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species
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Watanabe, K. P., primary, Kawai, Y. K., additional, Nakayama, S. M. M., additional, Ikenaka, Y., additional, Mizukawa, H., additional, Takaesu, N., additional, Ito, M., additional, Ikushiro, S.-I., additional, Sakaki, T., additional, and Ishizuka, M., additional
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- 2014
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14. Effects of uniaxial stress on local vibration of a platinum‐hydrogen complex in silicon
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Kamiura, Y., primary, Higaki, K., additional, Katayama, K., additional, Mizukawa, H., additional, Ishiyama, T., additional, Yamashita, Y., additional, and Abe, S., additional
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- 2010
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15. Distribution of hydroxyapatite crystallite orientation and ultrasonic wave velocity in ring-shaped cortical bone of bovine femur
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Yamato, Yu., primary, Matsukawa, M., additional, Mizukawa, H., additional, Yanagitani, T., additional, Yamazaki, K., additional, and Nagano, A., additional
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- 2008
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16. Incidence and public health risk assessment of toxic metal residues (cadmium and lead) in Egyptian cattle and sheep meats.
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Darwish, W. S., Hussein, M. A., El-Desoky, K. I., Ikenaka, Y., Nakayama, S., Mizukawa, H., and Ishizuka, M.
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HEALTH risk assessment ,POLLUTION ,HEAVY metals ,FOOD contamination - Abstract
Environmental pollution by heavy metals is a serious problem worldwide. This study aimed to investigate comparisons between concentrations of toxic metals (cadmium and lead) in the liver, kidneys, and muscle of Egyptian cattle and sheep. The effect of animal age on levels of toxic metal residues as well as results of a public health risk assessment is also reported. The results show that both cadmium and lead levels exceeded Food and Agriculture Organization and World Health Organization permissible limits in the liver and kidneys. These parts had higher concentrations of toxic metals compared with muscle in the two animal species examined. Age had a significant influence on toxic metal accumulation in both species. The hazard index indicates that consuming the livers and kidneys of these animals might pose a health risk. [ABSTRACT FROM AUTHOR]
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- 2015
17. P3F-8 Elastic Anisotropy and Crystallites Orientation in Bovine Cortical Bone
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Matsukawa, M., primary, Yanagitani, T., additional, Mizukawa, H., additional, Yamato, Y., additional, Yamazaki, K., additional, and Nagano, A., additional
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- 2006
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18. Walking Control of Humanoid Robot Based on Estimation and Control of Impulse
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Mizukawa, H., primary and Nakamura, Y., additional
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- 2003
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19. P3F-8 Elastic Anisotropy and Crystallites Orientation in Bovine Cortical Bone.
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Mizukawa, H., Matsukawa, M., Yamato, Y., Yamazaki, K., Nagano, A., and Yanagitani, T.
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- 2006
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20. Effects of uniaxial stress on local vibration of a platinum-hydrogen complex in silicon.
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Kamiura, Y., Higaki, K., Katayama, K., Mizukawa, H., Ishiyama, T., Yamashita, Y., and Abe, S.
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- 2011
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21. Inhibition by singlet molecular oxygen of the vascular reactivity in rabbit mesenteric artery.
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Mizukawa, H and Okabe, E
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- 1997
22. Incidence and public health risk assessment of toxic metal residues (cadmium and lead) in Egyptian cattle and sheep meats
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Darwish, W. S., Mohamed Hussein, El-Desoky, K. I., Ikenaka, Y., Nakayama, S., Mizukawa, H., and Ishizuka, M.
23. Mechanism and Problem of Warp Knit Machines with Weft Insertion
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Mizukawa, H., primary
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- 1973
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24. Serum trehalase activity in patients with rheumatoid arthritis
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Yoshida, K., Mizukawa, H., and Haruki, E.
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- 1993
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25. In vivo observation of velocity of vibration in uterus using forced vibration ultrasonic imaging system
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Kobayashi, K., Okai, T., Mizuno, M., Fujisawa, S., Mizukawa, H., Fujii, K., Ninoyu, H., Jhang, K.Y., Sato, T., and Yamakoshi, Y.
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- 1992
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26. Investigation of Functional Cytochrome P450 4A Enzymes in Liver and Kidney of Pigs, Cats, Tree Shrews, and Dogs in Comparison with the Metabolic Capacity of Human P450 4A11.
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Uno Y, Tsukiyama-Kohara K, Ishizuka M, Mizukawa H, Murayama N, and Yamazaki H
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- Animals, Humans, Dogs, Swine, Cats, Cytochrome P-450 Enzyme System metabolism, Cytochrome P-450 Enzyme System genetics, DNA, Complementary genetics, Molecular Sequence Data, Species Specificity, Liver metabolism, Liver enzymology, Cytochrome P-450 CYP4A metabolism, Cytochrome P-450 CYP4A genetics, Kidney metabolism, Amino Acid Sequence, Tupaiidae genetics, Phylogeny
- Abstract
Pigs are sometimes used in preclinical drug metabolism studies, with growing interest, and thus their drug-metabolizing enzymes, including the cytochromes P450 (P450 or CYP; EC 1.14.14.1), need to be examined. In the present study, novel CYP4A cDNAs were isolated and characterized, namely, pig CYP4A23 and CYP4A90; cat CYP4A37 and CYP4A106; and tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g. For comparison, the following known CYP4A cDNAs were also analyzed: pig CYP4A21 and dog CYP4A37, CYP4A38, and CYP4A39. These CYP4A cDNAs all contained open reading frames of 504-513 amino acids and had high amino acid sequence identity (74%-80%) with human CYP4As. Phylogenetic analysis of amino acid sequences revealed that these CYP4As were clustered in each species. All CYP4A genes contained 12 coding exons and formed a gene cluster in the corresponding genomic regions. A range of tissue types were analyzed, and these CYP4A mRNAs were preferentially expressed in liver and/or kidney, except for pig CYP4A90, which showed preferential expression in lung and duodenum. CYP4A enzymes, heterologously expressed in Escherichia coli , preferentially catalyzed lauric acid 12-hydroxylation and arachidonic acid 20-hydroxylation, just as human CYP4A11 does, with the same regioselectivity (i.e., at the ω -position of fatty acids). These results imply that dog, cat, pig, and tree shrew CYP4As have functional characteristics similar to those of human CYP4A11, with minor differences in lauric acid 12-hydroxylation. SIGNIFICANCE STATEMENT: Cytochrome P450 (P450, CYP) 4As are important P450s in human biological processes because of their fatty acid-metabolizing ability. Pig CYP4A21, CYP4A23, and CYP4A90; cat CYP4A37 and CYP4A106; tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g; and dog CYP4A37, CYP4A38, and CYP4A39 cDNAs were isolated and analyzed. These CYP4A cDNAs shared relatively high sequence identities with human CYP4A11 and CYP4A22. Pig, cat, tree shrew, and dog CYP4As in the liver and kidneys are likely to catalyze the ω -hydroxylation of fatty acids., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)
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- 2024
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27. Surveys of eleven species of wild and zoo birds and feeding experiments in white-tailed eagles reveal differences in the composition of the avian gut microbiome based on dietary habits between and within species.
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Ogasawara K, Yamada N, Nakayama SM, Watanabe Y, Saito K, Chiba A, Uchida Y, Ueda K, Takenaka Y, Kazama K, Kazama M, Yamagishi J, Mizukawa H, Ikenaka Y, and Ishizuka M
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- Animals, Bacteria genetics, Diet veterinary, Feces microbiology, Feeding Behavior, RNA, Ribosomal, 16S genetics, Gastrointestinal Microbiome genetics, Eagles, Deer genetics
- Abstract
The composition of the gut microbiome varies due to dietary habits. We investigated influences of diet on the composition of the gut microbiome using the feces of 11 avian species, which consumed grain-, fish- and meat-based diets. We analyzed gut microbiome diversity and composition by next-generation sequencing (NGS) of 16S ribosomal RNA. The grain-diet group had higher gut microbiome diversity than the meat- and fish-diet group. The ratio of Bacteroidetes and Firmicutes phyla was higher in the grain-diet group than in the meat- and fish-diet groups. The grain-diet group had a higher ratio of Veillonellaceae than the meat-diet group and a higher ratio of Eubacteriaceae than the fish-diet habit group. To clarify the influence of diet within the same species, white-tailed eagles (Haliaeetus albicilla, n=6) were divided into two groups, and given only deer meat or fish for approximately one month. The composition of the gut microbiome of individuals in both groups were analyzed by NGS. There were indications of fluctuation in the levels of some bacteria (Lactobacillus, Coriobacteriales, etc.) in each diet group. Moreover, one individual for each group which switched each diet in last week changed to each feature of composition of bacterial flora. The above results show that the composition of the gut microbiome differ depending on diet, even within the same species.
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- 2023
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28. Adverse effects of contamination by fipronil and its derivatives on growth, molting, and gene expression in the mysid crustacean, Americamysis bahia, in Japanese estuaries.
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Uchida M, Mizukawa H, Hirano M, Tominaga N, Arizono K, and Ishibashi H
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- Animals, Chromatography, Liquid, Estuaries, Gene Expression, Japan, Tandem Mass Spectrometry, Water analysis, Crustacea drug effects, Crustacea genetics, Crustacea growth & development, Molting, Water Pollutants, Chemical analysis, Water Pollutants, Chemical toxicity
- Abstract
Concentrations of fipronil (Fip) and several of its derivatives were detected in samples from four rivers and four estuaries in Japan. LC-MS/MS analysis detected Fip and its derivatives, except for fipronil detrifluoromethylsulfinyl, in almost all samples. The total concentrations of the five compounds were approximately two-fold greater in river water (mean: 21.2, 14.1, and 9.95 ng/L in June, July, and September, respectively) compared to those in estuarine water (mean: 10.3, 8.67, and 6.71 ng/L, respectively). Fipronil, fipronil sulfone (Fip-S), and fipronil sulfide (Fip-Sf) represented more than 70 % of all compounds. This is the first report to demonstrate the contamination of estuarine waters of Japan by these compounds. We further investigated the potentially toxic effects of Fip, Fip-S, and Fip-Sf on the exotic mysid, Americamysis bahia (Crustacea: Mysidae). The lowest effective concentrations of Fip-S (10.9 ng/L) and Fip-Sf (19.2 ng/L) on mysid growth and molting was approximately 12.9- and 7.3-fold lower than Fip (140.3 ng/L), suggesting they had higher toxicity. Quantitative reverse transcription polymerase chain reaction analysis revealed that ecdysone receptor and ultraspiracle gene expression were not affected after 96-h of exposure to Fip, Fip-S, and Fip-Sf, suggesting that these genes may not be involved in the molting disruption induced by Fip, Fip-S, and Fip-Sf. Our findings suggest that environmentally relevant concentrations of Fip and its derivatives can disrupt the growth of A. bahia by promoting molting. However, further studies are required to elucidate its molecular mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
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- 2023
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29. Occurrence, potential sources, and risk assessment of pharmaceuticals and personal care products in atmospheric particulate matter in Hanoi, Vietnam.
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Duong HT, Kadokami K, Nguyen DT, Trinh HT, Doan NH, Mizukawa H, and Takahashi S
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- Child, Adult, Humans, Particulate Matter analysis, Environmental Monitoring methods, Vietnam, Risk Assessment, Pharmaceutical Preparations, Cosmetics, Water Pollutants, Chemical
- Abstract
Pharmaceutical and personal care products (PCPPs) were recently recognized as emerging pollutants due to their potential for adverse health and environmental impacts. One potential route of exposure, atmospheric particulate matter (APM), for polar PPCP chemicals has to date received limited attention. This study screened for 190 polar PPCP chemicals in outdoor APM samples collected from two locations in Hanoi, Vietnam, and predictions of source and potential effects on human health are presented. Day and night, as well as dry and rainy seasonal samples, were taken, and samples screened by LC-TOF, using sequential window acquisition and all theoretical fragment ion spectra method. Eleven PPCP chemicals were detected above the LOD and in more than one sample. The ∑11PPCP chemicals ranged from 0.61 to 21.9 ng m
-3 (median 2.07 ng m-3 ), with between 2 and 6 compounds identified in individual samples (median 4). The ∑11PPCP chemicals collected near a heavy traffic area was greater than that in a populated residential zone. Night concentrations were significantly greater than day in both dry and rainy seasons (p < 0.05). Butyl methoxydibenzoylmethane, benzophenone-3, acetaminophen, cotinine, and fluorescent brightener 71 were detected in > 50% of samples. These are typically found in sunscreens, cosmetics, antipyretics, tobacco, and dyes. The DIair , hazard quotient (HQ), and hazard index (HI) for adults and children at sampling sites were estimated. The HQ for both adults and children were orders of magnitude less than the risk or were close to or whichever. APM does appear to be a potential additional secondary exposure source of PPCP chemicals to the environment and more work is needed to identify if sources are local or ubiquitous and if there is a greater health risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2023
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30. Biological effects related to exposure to polychlorinated biphenyl (PCB) and decabromodiphenyl ether (BDE-209) on cats.
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Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Takiguchi M, Tanabe S, and Ishizuka M
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- Male, Cats, Humans, Animals, Halogenated Diphenyl Ethers toxicity, Liver metabolism, Thyroid Hormones, Polychlorinated Biphenyls toxicity, Polychlorinated Biphenyls metabolism
- Abstract
As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Khidkhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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31. Sulfotransferases (SULTs), enzymatic and genetic variation in Carnivora: Limited sulfation capacity in pinnipeds.
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Kondo M, Ikenaka Y, Nakayama SMM, Kawai YK, Mizukawa H, Mitani Y, Nomyama K, Tanabe S, and Ishizuka M
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- Animals, Sulfotransferases genetics, Sulfotransferases metabolism, Inactivation, Metabolic, Genetic Variation, Xenobiotics metabolism, Caniformia metabolism
- Abstract
Wild carnivorans are one of the most important species due to their high positions in the food chain. They are also highly affected by numerous environmental contaminants through bioaccumulation and biomagnification. Xenobiotic metabolism is a significant chemical defense system from xenobiotics because it degrades the activity of a wide range of chemicals, generally into less active forms, resulting in their deactivation. Sulfotransferases (SULTs) are one of the most important xenobiotic metabolic enzymes, which catalyze the sulfonation of a variety of endogenous and exogenous chemicals, such as hormones, neurotransmitters, and a wide range of xenobiotic compounds. Although SULTs are of such high importance, little research has focused on these enzymes in wild carnivorans. In this study, we clarified the genetic properties of SULTs in a wide range of mammals, focusing on carnivorans, using in silico genetic analyses. We found genetic deficiencies of SULT1E1 and SULT1D1 isoforms in all pinnipeds analyzed and nonsense mutations in SULT1Cs in several carnivorans including pinnipeds. We further investigated the enzymatic activity of SULT1E1 in vitro using liver cytosols from pinnipeds. Using a SULT1E1 probe substrate, we found highly limited estradiol sulfonation in pinnipeds, whereas other mammals had relatively high sulfation. These results suggest that pinnipeds have severely or completely absent SULT1E1 activity, which importantly catalyzes the metabolism of estrogens, drugs, and environmental toxins. This further implies a high susceptibility to a wide range of xenobiotics in these carnivorans, which are constantly exposed to environmental chemicals throughout their lifetime., Competing Interests: Declaration of competing interest Authors have disclosed any potential conflict of interest, financial or personal, or declared that there are none to disclose, in relation to the publishing of the research., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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32. Contamination Status of Pet Cats in Thailand with Organohalogen Compounds (OHCs) and Their Hydroxylated and Methoxylated Derivatives and Estimation of Sources of Exposure to These Contaminants.
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Shimasaki M, Mizukawa H, Takaguchi K, Saengtienchai A, Ngamchirttakul A, Pencharee D, Khidkhan K, Ikenaka Y, Nakayama SMM, Ishizuka M, and Nomiyama K
- Abstract
In this study, we analyzed serum samples of pet cats from Thailand and estimated the contribution to organohalogen compounds (OHCs) exposure through cat food and house dust intake. BDE-209 was predominant in cat sera and accounted for 76% of all polybrominated diphenyl ethers (PBDEs). Decabromodiphenyl ether (BDE-209) is a major contaminant in dry cat food and house dust, which has been estimated to be a source of exposure for Thai pet cats. BDE-209 is a major contaminant of OHCs in dry cat food and house dust, which was estimated to be a source of exposure for Thai pet cats. On the other hand, the level of contamination by PCBs was lower than in other countries. Analysis of pet foods suggested that BDE-209 in pet cat serum was attributable to the consumption of dry cat food. On the other hand, house dust also contained high concentrations of BDE-209. Thus, high levels of BDE-209 in pet cat sera can be attributed to the consumption of dry cat food and house dust. These results suggest that pet cats are routinely exposed to non-negligible levels of OHCs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data.
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- 2022
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33. Ureteral morphology and pathology during urolithiasis in cats.
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Ichii O, Oyamada K, Mizukawa H, Yokoyama N, Namba T, Otani Y, Elewa YHA, Sasaki N, Nakamura T, and Kon Y
- Subjects
- Animals, Cats, Collagen, Inflammation pathology, Inflammation veterinary, Cat Diseases pathology, Ureter pathology, Ureteral Obstruction pathology, Ureteral Obstruction veterinary, Urolithiasis veterinary
- Abstract
Cats exhibit high susceptibility to urinary organ-related diseases. We investigated the healthy ureter morphologies and compared these with ureters that were surgically resected distal to a urolithiasis obstruction in cats. Healthy ureters (total length 9.88 ± 0.38 cm) developed adventitia composed of collagen fibers (ADCF), containing a longitudinal muscular layer, toward the distal segment. The healthy ureter was the smallest in the middle segment (4.71-6.90 cm from the urinary bladder) with significantly decreased luminal and submucosal areas compared to those in the proximal segment. Diseased cats exhibited a high incidence of calcium oxalate urolithiasis with renal dysfunction, regardless of age, sex, and body size. Diseased ureters showed increased perimeters, inflammation, and decreased nerves in ADCF. Collagen fibers were increased in the submucosal area, intermuscular spaces, and ADCF, particularly near the obstructed lesion. The mean resected ureter length was 5.66 ± 0.49 cm, suggesting a high obstruction risk in the middle segment. The middle segment also increased the cross-sectional area of the ureter and ADCF, regardless of the distance from the obstructed lesion. The ureters in several cases either lacked the transitional epithelium, or exhibited transitional epithelial hyperplasia, and some of these formed the mucosal folds. In conclusion, we demonstrated the following characteristics and histopathological features of cat ureters: decreases in the ureter size, lumen area, and submucosa area from proximal to middle segment in healthy; ADCF changes in urolithiasis, including increased connective tissues with inflammation and decreased nerves. These data are important to understand the pathogenesis of feline ureteral obstruction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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34. Cytochrome P450 2J Genes Are Expressed in Dogs, Cats, and Pigs, and Encode Functional Drug-Metabolizing Enzymes.
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Uno Y, Murayama N, Ijiri M, Kawaguchi H, Yamato O, Shiraishi M, Asano A, Teraoka H, Mizukawa H, Nakayama SMM, Ikenaka Y, Ishizuka M, and Yamazaki H
- Subjects
- Animals, Astemizole, Butyrophenones, Cytochrome P-450 CYP2J2, Humans, Phylogeny, Piperidines, Terfenadine, Cats genetics, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Dogs genetics, Swine genetics
- Abstract
Cytochrome P450s (P450s) have been identified and analyzed in dogs and pigs, species that are often used in preclinical drug studies. Moreover, P450s are clinically important for drug therapy not only in humans, but also in species under veterinary care, including dogs and cats. In the present study, seven P450s homologous to human CYP2J2, namely, dog CYP2J2; cat CYP2J2; and pig CYP2J33, CYP2J35, CYP2J91, and CYP2J93, were newly identified and characterized, along with pig CYP2J34 previously identified. The cDNAs of these CYP2Js contain open reading frames of 502 amino acids, except for CYP2J35 (498 amino acids), and share high sequence identity (77%-80%) with human CYP2J2. Phylogenetic analysis revealed that dog and cat CYP2J2 were closely related, whereas pig CYP2Js formed a cluster. All seven CYP2J genes contain nine coding exons and are located in corresponding genomic regions, with the pig CYP2J genes forming a gene cluster. These CYP2J2 mRNAs were predominantly expressed in the small intestine with additional expression in the kidney and brain for dog CYP2J2 and pig CYP2J91 mRNAs, respectively. All seven CYP2Js metabolized human CYP2J2 substrates terfenadine, ebastine, and astemizole, indicating that they are functional enzymes. Dog CYP2J2 and pig CYP2J34 and CYP2J35 efficiently catalyzed ebastine primary hydroxylation and secondary carebastine formation at low substrate concentrations, just as human CYP2J2 does. Velocity - versus-substate plots exhibited sigmoidal relationships for dog CYP2J2, cat CYP2J2, and pig CYP2J33, indicating allosteric interactions. These results suggest that dog, cat, and pig CYP2Js have similar functional characteristics to human CYP2J2, with slight differences in ebastine and astemizole oxidations. SIGNIFICANCE STATEMENT: Dog CYP2J2; cat CYP2J2; and pig CYP2J33, CYP2J34, CYP2J35, CYP2J91, and CYP2J93, homologous to human CYP2J2, were identified and characterized by sequence, phylogenetic, and genomic structure analyses. Intestinal expression patterns of CYP2J mRNAs were characteristic in dogs, cats, and pigs. Dog, cat, and pig CYP2Js likely play roles as drug-metabolizing enzymes in the small intestine, similar to human CYP2J2., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)
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- 2022
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35. Health impact assessment of pet cats caused by organohalogen contaminants by serum metabolomics and thyroid hormone analysis.
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Nomiyama K, Yamamoto Y, Eguchi A, Nishikawa H, Mizukawa H, Yokoyama N, Ichii O, Takiguchi M, Nakayama SMM, Ikenaka Y, and Ishizuka M
- Subjects
- Animals, Cats, Halogenated Diphenyl Ethers metabolism, Health Impact Assessment, Humans, Metabolomics, Thyroid Hormones, Environmental Pollutants toxicity, Polychlorinated Biphenyls metabolism
- Abstract
Companion animals are in close contact with the human surroundings, and there is growing concern about the effects of harmful substances on the health of pet cats. In this study, we investigated the potential health effects of organohalogen compounds (OHCs) on thyroid hormone (TH) homeostasis and metabolomics in Japanese pet cats. There was a significant negative correlation between concentrations of several contaminants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), hydroxylated PCBs (OH-PCBs), hydroxylated PBDEs (OH-PBDEs), and THs in cat serum samples. These results suggested that exposure to OHCs causes a decrease in serum TH levels in pet cats. In this metabolomics study, each exposure level of parent compounds (PCBs and PBDEs) and their hydroxylated compounds (OH-PCBs and OH-PBDEs) were associated with their own unique primary metabolic pathways, suggesting that parent and phenolic compounds exhibit different mechanisms of action and biological effects. PCBs were associated with many metabolic pathways, including glutathione and purine metabolism, and the effects were replicated in in-vivo cat PCB administration studies. These results demonstrated that OHC exposure causes chronic oxidative stress in pet cats. PBDEs were positively associated with alanine, aspartate, and glutamate metabolism. Due to the chronic exposure of cats to mixtures of these contaminants, the combination of their respective metabolic pathways may have a synergistic effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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36. Editorial: Animal Poisoning and Biomarkers of Toxicity.
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Capela E Silva F, Sousa AC, Pastorinho MR, Mizukawa H, and Ishizuka M
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2022
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37. Geolocators link marine mercury with levels in wild seabirds throughout their annual cycle: Consequences for trans-ecosystem biotransport.
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Shoji A, Elliott KH, Watanuki Y, Basu N, Whelan S, Cunningham J, Hatch S, Mizukawa H, Nakayama SMM, Ikenaka Y, Ishizuka M, and Aris-Brosou S
- Subjects
- Alaska, Animals, Birds, Ecosystem, Environmental Monitoring, Feathers chemistry, Plant Breeding, Mercury analysis
- Abstract
Seabirds are widely used as indicators of marine pollution, including mercury (Hg), because they track contaminant levels across space and time. However, many seabirds are migratory, and it is difficult to understand the timing and location of their Hg accumulation. Seabirds may obtain Hg thousands of kilometers away, during their non-breeding period, and deposit that Hg into their terrestrial breeding colonies. We predicted that Hg concentration in rectrices reflects exposure during the previous breeding season, in body feathers reflects non-breeding exposure, and in blood collected during breeding reflects exposure during current breeding. To test this hypothesis, we measured total Hg concentration in these three tissues, which reflect different timepoints during the annual cycle of rhinoceros auklets (Cerorhinca monocerata) breeding on both sides of the North Pacific (Middleton Island in Alaska and Teuri Island in Hokkaido), and tracked their wintering movement patterns with biologging devices. We (i) identify the wintering patterns of both populations, (ii) examine Hg levels in different tissues representing exposure at different time periods, (iii) test how environmental Hg exposure during the non-breeding season affects bird contamination, and (iv) assess whether variation in Hg levels during the non-breeding season influences levels accumulated in terrestrial plants. Individuals from both populations followed a figure-eight looping migration pattern. We confirm the existence of a pathway from environmental Hg to plant roots via avian tissues, as Hg concentrations were higher in plants within the auklet colonies than at control sites. Hg concentrations of breast feathers were higher in Alaskan than in Japanese auklets, but Hg concentrations in rectrices and blood were similar. Moreover, we found evidence that tissues with different turnover rates could record local anthropogenic Hg emission rates of areas visited during winter. In conclusion, Hg was transported across thousands of kilometers by seabirds and transferred to local plants., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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38. The effects of fipronil on emotional and cognitive behaviors in mammals.
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Suzuki T, Hirai A, Khidkhan K, Nimako C, Ichise T, Takeda K, Mizukawa H, Nakayama SMM, Nomiyama K, Hoshi N, Maeda M, Hirano T, Sasaoka K, Sasaki N, Takiguchi M, Ishizuka M, and Ikenaka Y
- Subjects
- Animals, Cats, Cognition, Dogs, Mammals, Mice, Pyrazoles, Rats, Cat Diseases, Dog Diseases, Insecticides toxicity
- Abstract
Fipronil is a phenylpyrazole insecticide that is widely used as a pesticide and a veterinary drug, although studies suggest that it could be toxic to mammals. The objectives of this study were to examine the pharmacokinetic profile of fipronil in mice, dogs, and cats, and to evaluate its effects on emotional and cognitive behaviors of dogs and cats using the data obtained from mice. The assessment of in vivo kinetics of fipronil was conducted in mice and dogs. We also performed behavioral tests (elevated plus-maze and Y-maze) and measured the levels of neurotransmitters in mice exposed to fipronil. In addition, the in vitro metabolism of fipronil were evaluated using liver microsomes of rats, mice, dogs, and cats. The results revealed that fipronil is distributed throughout the body (blood, brain, adipose tissue, and liver) of mice after dermal application. It was metabolized to fipronil sulfone primarily in the liver. The data on kinetics show that both fipronil and fipronil sulfone have a longer half-life in dogs and cats than in mice. The behavioral tests indicated that fipronil and fipronil sulfone could affect emotional and cognitive behaviors and alter the levels of neurotransmitters (dopamine in the striatum and serotonin in the hippocampus) in mice. Furthermore, we found that dogs and cats have a low ability to metabolize fipronil than mice and rats. However, further comprehensive studies are needed to determine whether fipronil affects the emotional and cognitive behaviors when administered to dogs and cats. To the best of our knowledge, this is the first study to examine the pharmacokinetic data and verify the effects of fipronil on emotional and cognitive behaviors of dogs and cats using the data obtained from mice., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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39. Interspecies differences in cytochrome P450-mediated metabolism of neonicotinoids among cats, dogs, rats, and humans.
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Khidkhan K, Ikenaka Y, Ichise T, Nakayama SMM, Mizukawa H, Nomiyama K, Iwata H, Arizono K, Takahashi K, Kato K, and Ishizuka M
- Subjects
- Animals, Cats, Dogs, Humans, Microsomes, Liver metabolism, Oxidation-Reduction, Rats, Rats, Sprague-Dawley, Species Specificity, Cytochrome P-450 Enzyme System metabolism, Insecticides metabolism, Insecticides toxicity, Neonicotinoids metabolism, Neonicotinoids toxicity
- Abstract
Neonicotinoid insecticides are used for agricultural and non-agricultural purposes worldwide. Pets are directly exposed to neonicotinoids in veterinary products and through environmental contamination. Cytochrome P450 (CYP) is among the most significant xenobiotic metabolizing enzymes that oxidizes several chemicals, including neonicotinoids. However, CYP activities and metabolite compositions of neonicotinoid metabolites are unknown in most domesticated pet species. Our objectives were to reveal the differences in metabolites of neonicotinoids (imidacloprid, clothianidin, and acetamiprid) and CYP activities among common pet species (cats and dogs), humans, and rats. The results indicated that the CYP-mediated neonicotinoid metabolism was different depending on species and each neonicotinoid. Among these four species, the kinetics of imidacloprid metabolism indicated that rats have the highest rate of oxidation of imidacloprid to 4OH-imidacloprid, while the greatest enzyme kinetics of imidacloprid metabolism to 5OH-imidacloprid were found in rats and humans. Clothianidin was rapidly metabolized to 1-methyl-3-nitroguanidine and dm-clothianidin in rats, but cats and humans showed the lowest formation of dm-clothianidin. CYP activities in metabolism of acetamiprid to dm-acetamiprid and N-acetyl-acetamiprid were determined to be significantly higher in humans compared to other species. However, further studies should be targeted at identifying the differences in hepatic metabolism of neonicotinoids in these species using recombinant CYP enzymes., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2021
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40. Altered hepatic cytochrome P450 expression in cats after chronic exposure to decabromodiphenyl ether (BDE-209).
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Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Takiguchi M, Tanabe S, and Ishizuka M
- Subjects
- Animals, Cats, Cytochrome P-450 Enzyme System genetics, Liver metabolism, Male, RNA, Messenger metabolism, Toxicity Tests, Chronic veterinary, Cytochrome P-450 Enzyme System metabolism, Halogenated Diphenyl Ethers toxicity, Liver enzymology
- Abstract
The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in clinical applications for the medication and prediction of adverse effects. The aim of this study was to evaluate the mRNA expression of CYP1-CYP3 families in cats exposed to BDE-209 for one year. All selected CYP isoforms showed no significant difference in mRNA expressions between control and exposure groups, however, CYP3A12 and CYP3A131 revealed tend to be two times higher in the exposure group compared to control group. The present results indicate that the chronic exposure of BDE209 could not alter CYP expression in the liver of cats. This result considered caused by the deficiency of CYP2B subfamily which is major metabolism enzyme of polybrominated diphenyl ethers (PBDEs) in cat.
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- 2020
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41. In Vivo Accumulation of Plastic-Derived Chemicals into Seabird Tissues.
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Tanaka K, Watanuki Y, Takada H, Ishizuka M, Yamashita R, Kazama M, Hiki N, Kashiwada F, Mizukawa K, Mizukawa H, Hyrenbach D, Hester M, Ikenaka Y, and Nakayama SMM
- Subjects
- Animals, Aquatic Organisms metabolism, Environmental Exposure, Environmental Monitoring, Birds metabolism, Plastics metabolism, Water Pollutants, Chemical metabolism
- Abstract
Plastic debris is ubiquitous and increasing in the marine environment [1]. A wide range of marine organisms ingest plastic, and its impacts are of growing concern [2]. Seabirds are particularly susceptible to plastic pollution because of high rates of ingestion [3]. Because marine plastics contain an array of hazardous compounds, the chemical impacts of ingestion are concerning. Several studies on wild seabirds suggested accumulation of plastic-derived chemicals in seabird tissues [4-7]. However, to date, the evidence has all been indirect [4-7], and it is unclear whether plastic debris is the source of these pollutants. To obtain direct evidence for the transfer and accumulation of plastic additives in the tissues of seabirds, we conducted an in vivo plastic feeding experiment. Environmentally relevant exposure of plastics compounded with one flame retardant and four ultraviolet stabilizers to streaked shearwater (Calonectris leucomelas) chicks in semi-field conditions resulted in the accumulation of the additives in liver and adipose fat of 91 to 120,000 times the rate from the natural diet. Additional monitoring of six seabird species detected these chemical additives only in those species with high plastic ingestion rates, suggesting that plastic debris can be a major pathway of chemical pollutants into seabirds. These findings provide direct evidence of seabird exposure to plastic additives and emphasize the role of marine debris ingestion as a source of chemical pollution in marine organisms., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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42. Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1.
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Nakayama SMM, Morita A, Ikenaka Y, Kawai YK, Watanabe KP, Ishii C, Mizukawa H, Yohannes YB, Saito K, Watanabe Y, Ito M, Ohsawa N, and Ishizuka M
- Subjects
- Amino Acid Sequence genetics, Animals, Mutation, RNA, Messenger biosynthesis, Species Specificity, Vitamin K Epoxide Reductases chemistry, Vitamin K Epoxide Reductases genetics, Anticoagulants poisoning, Canaries genetics, Drug Resistance genetics, Raptors genetics, Rodenticides poisoning, Vitamin K Epoxide Reductases antagonists & inhibitors, Warfarin poisoning
- Abstract
Worldwide use of anticoagulant rodenticides (ARs) for rodents control has frequently led to secondary poisoning of non-target animals, especially raptors. In order to suggest some factors that may help considering the mechanism of the incidents, this study focused on the avian vitamin K 2, 3-epoxide reductase (VKOR) that is the target protein of ARs. We addressed the interspecific differences in VKOR activity and inhibition related to amino acid sequence and mRNA expression of VKORC1 and VKORC1-like1 (VKORC1L1). Poultry have been considered to be more tolerant to ARs than mammals. However, VKOR activity of owls, hawks, falcon and surprisingly, canaries, was lower and inhibited by warfarin more easily than that of chickens and turkeys. The amino acid sequence of VKORC1 and VKORC1L1 implied that the value of Ki for VKOR activity to ARs could depend on the amino acid at position 140 in the TYX warfarin-binding motif in VKORC1, and other amino acid mutations in VKORC1L1. The mRNA expression ratio of VKORC1:VKORC1L1 differed between turkey (8:1) and chicken (2:3) liver. VKORC1L1 has been reported to be resistant to warfarin compared to VKORC1. Hence, both the Ki of specific VKORC1 and VKORC1L1, and the mRNA expression ratio would cause avian interspecific difference of the VKOR inhibition. Our study also suggested the high inhibition of VKOR activities in raptors and surprisingly that in canaries as well. These factors are the most likely to contribute to the high sensitivity to ARs found in raptors., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2020
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43. Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry.
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Togao M, Nakayama SMM, Ikenaka Y, Mizukawa H, Makino Y, Kubota A, Matsukawa T, Yokoyama K, Hirata T, and Ishizuka M
- Subjects
- Animals, Brain metabolism, Immunohistochemistry methods, Laser Therapy, Male, Mass Spectrometry methods, Mice, Mice, Inbred BALB C, Spectrum Analysis, Brain Chemistry drug effects, Kidney chemistry, Lead analysis, Liver chemistry, Stromal Interaction Molecule 1 analysis
- Abstract
Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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44. Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure.
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Khidkhan K, Mizukawa H, Ikenaka Y, Nakayama SMM, Nomiyama K, Yokoyama N, Ichii O, Darwish WS, Takiguchi M, Tanabe S, and Ishizuka M
- Subjects
- Animals, Cats, Liver metabolism, Male, Metabolic Detoxication, Phase I, Tissue Distribution, Cytochrome P450 Family 1 metabolism, Cytochrome P450 Family 2 metabolism, Cytochrome P450 Family 3 metabolism, Polychlorinated Biphenyls toxicity, Xenobiotics toxicity
- Abstract
Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in cats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1-CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1-CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3',4,4'-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3-4 Cl-PCBs, because a high hydroxylated metabolite level of 3-4 Cl-OH-PCBs was observed in the liver., (Copyright © 2019. Published by Elsevier Inc.)
- Published
- 2019
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45. Effects of the organochlorine p,p'-DDT on MCF-7 cells: Investigating metabolic and immune modulatory transcriptomic changes.
- Author
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Thompson LA, Ikenaka Y, Sobhy Darwish W, Nakayama SMM, Mizukawa H, and Ishizuka M
- Subjects
- Cell Survival drug effects, Humans, MCF-7 Cells, Multidrug Resistance-Associated Protein 2, DDT toxicity, Immunologic Factors toxicity, Insecticides toxicity, Transcriptome drug effects
- Abstract
The organochlorine pesticide dichloro-diphenyl-trichloroethane (DDT) is persistent in the environment and leads to adverse human health effects. High levels in breast milk pose a threat to both breast tissue and nursing infants. The objectives of this study were to investigate DDT-induced transcriptomic alterations in enzymes and transporters involved in xenobiotic metabolism, immune responses, oxidative stress markers, and cell growth in a human breast cancer cell line. MCF-7 cells were exposed to both environmentally-relevant and previously-tested concentrations of p,p'-DDT in a short-term experiment. Significant up-regulation of metabolizing enzymes and transporters (ACHE, GSTO1, NQO1 and ABCC2) and oxidative stress markers (CXCL8, HMOX-1, NFE2L2 and TNF) was clearly observed. Conversely, UGT1A6, AHR and cell growth genes (FGF2 and VEGFA) were severely down-regulated. Identification of these genes helps to identify mechanisms of p,p'-DDT action within cells and may be considered as useful biomarkers for exposure to DDT contamination., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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46. Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.
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Takaguchi K, Nishikawa H, Mizukawa H, Tanoue R, Yokoyama N, Ichii O, Takiguchi M, Nakayama SMM, Ikenaka Y, Kunisue T, Ishizuka M, Tanabe S, Iwata H, and Nomiyama K
- Subjects
- Animals, Cats, Dogs, Environmental Pollutants toxicity, Female, Male, Polychlorinated Biphenyls toxicity, Thyroxine blood, Environmental Pollutants metabolism, Polychlorinated Biphenyls metabolism, Thyroid Hormones blood
- Abstract
Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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47. Targeted metabolome analysis of the dog brain exposed to PCBs suggests inhibition of oxidative phosphorylation by hydroxylated PCBs.
- Author
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Nomiyama K, Eguchi A, Takaguchi K, Yoo J, Mizukawa H, Oshihoi T, Tanabe S, and Iwata H
- Subjects
- Adenosine Triphosphate metabolism, Animals, Dogs, Electron Transport Chain Complex Proteins metabolism, Environmental Pollutants chemistry, Environmental Pollutants metabolism, Hydroxylation, Male, Neurotoxins toxicity, Polychlorinated Biphenyls chemistry, Polychlorinated Biphenyls metabolism, Reactive Oxygen Species, Thyroid Hormones metabolism, Urea metabolism, Brain Chemistry drug effects, Environmental Pollutants toxicity, Metabolome, Oxidative Phosphorylation drug effects, Polychlorinated Biphenyls toxicity
- Abstract
Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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48. Temporal trends in PCB concentrations in mussels collected from areas affected by the Great East Japan Earthquake and Tsunami.
- Author
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Ishiyama M, Matsuo Y, Nakai K, Tatsuta N, Nakata H, Mizukawa H, Miyawaki T, Nagasaka H, Someya T, and Ueno D
- Subjects
- Animals, Japan, Water Pollutants, Chemical analysis, Bivalvia chemistry, Earthquakes, Environmental Monitoring, Polychlorinated Biphenyls analysis, Tsunamis
- Abstract
In the Great East Japan Earthquake of 11 March 2011, a magnitude 9.0 earthquake and accompanying tsunami struck the Tohoku region of Japan. The tsunami washed away old equipment containing polychlorinated biphenyls (PCBs) stored in the region's factories, and these PCBs may have leaked out of their casings into the marine environment. In this study, we evaluate marine PCB contamination by comparing mussels collected before (in 2005) and after (June 2011) the tsunami. PCB contamination levels were significantly elevated in mussel samples collected after the tsunami in June 2011 (3 months after the tsunami). This indicates that PCBs (specifically, formulation KC-400) leaked out of old equipment swept away by the tsunami and accumulated in mussels. PCBs were estimated to have an environmental half-life (EHL) in mussels of 4 months. Our results show that an earthquake and subsequent tsunami can cause elevated PCB contamination in the marine environment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
49. Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species.
- Author
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Kawai YK, Shinya S, Ikenaka Y, Saengtienchai A, Kondo M, Darwish WS, Nakayama SMM, Mizukawa H, and Ishizuka M
- Subjects
- Acetaminophen metabolism, Analgesics, Non-Narcotic metabolism, Animals, Birds metabolism, Glucuronosyltransferase genetics, Microsomes, Liver enzymology, Phylogeny, Species Specificity, Synteny, Birds genetics, Gene Expression Regulation, Enzymologic physiology, Glucuronosyltransferase metabolism
- Abstract
Birds are exposed to many xenobiotics during their lifetime. For accurate prediction of xenobiotic-induced toxic effects on avian species, it is necessary to understand metabolic capacities in a comprehensive range of bird species. However, there is a lack of information about avian xenobiotic metabolizing enzymes (XMEs), particularly in wild birds. Uridine diphosphate glucuronosyltransferase (UGT) is an XME that plays an important role in phase II metabolism in the livers of mammals and birds. This study was performed to determine the characteristics of UGT1E isoform in avian species, those are related to mammals UGT 1A. To understand the characteristics of avian UGT1E isoforms, in vitro metabolic activity and genetic characteristics were investigated. Furthermore, mRNA expression levels of all chicken UGT1E isoforms were measured. On in vitro enzymatic analysis, the white-tailed eagle, great horned owl, and Humboldt penguin showed lower UGT-dependent activity than domestic birds. In synteny analysis, carnivorous birds were shown to have fewer UGT1E isoforms than herbivorous and omnivorous birds, which may explain why they have lower in vitro UGT activity. These observations suggested that raptors and seabirds, in which UGT activity is low, may be at high risk if exposed to elevated levels of xenobiotics in the environment. Phylogenetic analysis suggested that avian UGT1Es have evolved independently from mammalian UGT1As. We identified the important UGT isoforms, such as UGT1E13, and suspected their substrate specificities in avian xenobiotic metabolism by phylogenetic and quantitative real-time PCR analysis. This is the first report regarding the genetic characteristics and interspecies differences of UGT1Es in avian species., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
50. A review: poisoning by anticoagulant rodenticides in non-target animals globally.
- Author
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Nakayama SMM, Morita A, Ikenaka Y, Mizukawa H, and Ishizuka M
- Subjects
- Animals, Animals, Wild, Poisoning epidemiology, Poisoning etiology, Raptors, Anticoagulants poisoning, Poisoning veterinary, Rodenticides poisoning
- Abstract
Worldwide use of anticoagulant rodenticides (ARs) for rodents control has frequently led to secondary poisoning of non-target animals, especially raptors. In spite of the occurrence of many incidents of primary or secondary AR-exposure and poisoning of non-target animals, these incidents have been reported only for individual countries, and there has been no comprehensive worldwide study or review. Furthermore, the AR exposure pathway in raptors has not yet been clearly identified. The aim of this review is therefore to comprehensively analyze the global incidence of primary and secondary AR-exposure in non-target animals, and to explore the exposure pathways. We reviewed the published literature, which reported AR residues in the non-target animals between 1998 and 2015, indicated that various raptor species had over 60% AR- detection rate and have a risk of AR poisoning. According to several papers studied on diets of raptor species, although rodents are the most common diets of raptors, some raptor species prey mainly on non-rodents. Therefore, preying on targeted rodents does not necessarily explain all causes of secondary AR-exposure of raptors. Since AR residue-detection was also reported in non-target mammals, birds, reptiles and invertebrates, which are the dominant prey of some raptors, AR residues in these animals, as well as in target rodents, could be the exposure source of ARs to raptors.
- Published
- 2019
- Full Text
- View/download PDF
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