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

Yosuke Uchiyama,Masahiko Takino,Michiko Noguchi,Nozomi Shiratori,Naoki Kobayashi,Yoshiko Sugita-Konishi

doi:10.3390/toxins11060360

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.

Highlights

Citreoviridin (CTVD) (Figure 1) is a mycotoxin produced as a secondary metabolite of Penicillium citreonigrum, Aspergillus terreus, and Eupenicillium ochrosalmoneum [1]
The toxicokinetics of CTVD were investigated in swine for extrapolation food habits
The toxicokinetics of CTVD were investigated in swine for extrapolation to to humans

Summary

Introduction

Citreoviridin (CTVD) (Figure 1) is a mycotoxin produced as a secondary metabolite of Penicillium citreonigrum, Aspergillus terreus, and Eupenicillium ochrosalmoneum [1]. Contamination with CTVD, well-known as yellow rice toxin, often occurs due to inappropriate management after harvest [7]. The toxicity of CTVD is mainly accompanied by ascending paralysis, central nervous system disturbance and respiratory arrest, and fatal adverse effects may occur [8]. Because CTVD is mainly found as a contaminant in rice, Toxins 2019, 11, 360; doi:10.3390/toxins11060360 www.mdpi.com/journal/toxins. Toxins 2019, 11, x FOR PEER REVIEW these properties of CTVD be a serious problem in which consume rice as a contaminant in rice, these can properties of CTVD can beina countries serious problem in people countries in which people staple food such as Thailand, Brazil, and Japan. Consume rice as a staple food such as Thailand, Brazil, and Japan.

Methods

Results

Conclusion