The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i>
Citreoviridin (CTVD), a mycotoxin called yellow rice toxin, is reported to be related to acute cardiac beriberi; however, its toxicokinetics remain unclear. The present study elucidated the toxicokinetics through in vivo experiments in swine and predicted the human toxicokinetics by comparing the fi...
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| Format: | Article |
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MDPI AG
2019-06-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/6/360 |
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| author | Yosuke Uchiyama Masahiko Takino Michiko Noguchi Nozomi Shiratori Naoki Kobayashi Yoshiko Sugita-Konishi |
| author_facet | Yosuke Uchiyama Masahiko Takino Michiko Noguchi Nozomi Shiratori Naoki Kobayashi Yoshiko Sugita-Konishi |
| author_sort | Yosuke Uchiyama |
| collection | DOAJ |
| description | Citreoviridin (CTVD), a mycotoxin called yellow rice toxin, is reported to be related to acute cardiac beriberi; however, its toxicokinetics remain unclear. The present study elucidated the toxicokinetics through in vivo experiments in swine and predicted the human toxicokinetics by comparing the findings to those from in vitro experiments. In vivo experiments revealed the high bioavailability of CTVD (116.4%) in swine. An intestinal permeability study using Caco-2 cells to estimate the toxicokinetics in humans showed that CTVD has a high permeability coefficient. When CTVD was incubated with hepatic S9 fraction from swine and humans, hydroxylation and methylation, desaturation, and dihydroxylation derivatives were produced as the predominant metabolites. The levels of these products produced using human S9 were higher than those obtained swine S9, while CTVD glucuronide was produced slowly in human S9 in comparison to swine S9. Furthermore, the elimination of CTVD by human S9 was significantly more rapid in comparison to that by swine S9. These results suggest that CTVD is easily absorbed in swine and that it remains in the body where it is slowly metabolized. In contrast, the absorption of CTVD in humans would be the same as that in swine, although its elimination would be faster. |
| first_indexed | 2024-04-11T20:39:35Z |
| format | Article |
| id | doaj.art-270f3e6e4aa64b4a887c200909ae9574 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T20:39:35Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-270f3e6e4aa64b4a887c200909ae95742022-12-22T04:04:14ZengMDPI AGToxins2072-66512019-06-0111636010.3390/toxins11060360toxins11060360The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i>Yosuke Uchiyama0Masahiko Takino1Michiko Noguchi2Nozomi Shiratori3Naoki Kobayashi4Yoshiko Sugita-Konishi5The Graduate School of Life and Environmental Sciences, Department of Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, JapanAgilent Technologies, Japan, Ltd., 9-1 Takakura-cho, Hachioji, Tokyo 192-8510, JapanLaboratory of Theriogenology, Department of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, JapanThe Graduate School of Life and Environmental Sciences, Department of Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, JapanThe Graduate School of Life and Environmental Sciences, Department of Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, JapanThe Graduate School of Life and Environmental Sciences, Department of Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, JapanCitreoviridin (CTVD), a mycotoxin called yellow rice toxin, is reported to be related to acute cardiac beriberi; however, its toxicokinetics remain unclear. The present study elucidated the toxicokinetics through in vivo experiments in swine and predicted the human toxicokinetics by comparing the findings to those from in vitro experiments. In vivo experiments revealed the high bioavailability of CTVD (116.4%) in swine. An intestinal permeability study using Caco-2 cells to estimate the toxicokinetics in humans showed that CTVD has a high permeability coefficient. When CTVD was incubated with hepatic S9 fraction from swine and humans, hydroxylation and methylation, desaturation, and dihydroxylation derivatives were produced as the predominant metabolites. The levels of these products produced using human S9 were higher than those obtained swine S9, while CTVD glucuronide was produced slowly in human S9 in comparison to swine S9. Furthermore, the elimination of CTVD by human S9 was significantly more rapid in comparison to that by swine S9. These results suggest that CTVD is easily absorbed in swine and that it remains in the body where it is slowly metabolized. In contrast, the absorption of CTVD in humans would be the same as that in swine, although its elimination would be faster.https://www.mdpi.com/2072-6651/11/6/360citreoviridintoxicokineticsbioavailabilityswineCaco-2S9 |
| spellingShingle | Yosuke Uchiyama Masahiko Takino Michiko Noguchi Nozomi Shiratori Naoki Kobayashi Yoshiko Sugita-Konishi The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> Toxins citreoviridin toxicokinetics bioavailability swine Caco-2 S9 |
| title | The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> |
| title_full | The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> |
| title_fullStr | The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> |
| title_full_unstemmed | The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> |
| title_short | The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from <i>Penicillium citreonigrum</i> |
| title_sort | in vivo and in vitro toxicokinetics of citreoviridin extracted from i penicillium citreonigrum i |
| topic | citreoviridin toxicokinetics bioavailability swine Caco-2 S9 |
| url | https://www.mdpi.com/2072-6651/11/6/360 |
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