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The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from Penicillium citreonigrum

1
The 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, Japan
2
Agilent Technologies, Japan, Ltd., 9-1 Takakura-cho, Hachioji, Tokyo 192-8510, Japan
3
Laboratory of Theriogenology, Department of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, Japan
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(6), 360; https://doi.org/10.3390/toxins11060360
Received: 3 June 2019 / Revised: 14 June 2019 / Accepted: 15 June 2019 / Published: 20 June 2019
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Abstract

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. View Full-Text
Keywords: citreoviridin; toxicokinetics; bioavailability; swine; Caco-2; S9 citreoviridin; toxicokinetics; bioavailability; swine; Caco-2; S9
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Uchiyama, Y.; Takino, M.; Noguchi, M.; Shiratori, N.; Kobayashi, N.; Sugita-Konishi, Y. The In Vivo and In Vitro Toxicokinetics of Citreoviridin Extracted from Penicillium citreonigrum. Toxins 2019, 11, 360.

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