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

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.

An in vitromodel to quantify interspecies differences in kinetics for intestinal microbial bioactivation and detoxification of zearalenone

“…In addition to having a high preference for the formation of α-ZEL, as shown also by Bravin et al [ 57 ], and in contrast to what was observed for the intestinal microbial metabolism, expressed per kg bw human hepatic metabolism appeared to show the highest in vivo k cat of the three species. The establishment of safe dose levels of exposure to ZEN for humans has been based on pigs as model species due to similarities in physiological and anatomical characteristics, as well as their efficient formation of α-ZEL [ 4 , 58 ], however, the higher preference for the bioactivation of ZEN shown in the present study together with the low preference for detoxification to β-ZEL, 4–6 times lower than α-ZEL formation, indicate a need for human-specific models to study metabolism and sensitivity to ZEN exposure. There is an urgent need for more human-relevant models in toxicology, as has also been demonstrated by the other researchers highlighting the differences in kinetics as an important contributor to species differences [ 59 ].…”

Chemical Constituents of the Deep-Sea-Derived Penicillium citreonigrum MCCC 3A00169 and Their Antiproliferative Effects

“…Penicillium citreonigrum is a commonly found fungus known for its contamination of rice with citreoviridin (CTV), a yellow mycotoxin related to the disease of acute cardiac beriberi [1]. In addition to CTV, P. citreonigrum can also produce other structurally diverse compounds, including azaphilones [2], chromones [3], alkaloids [3][4][5], sesquiterpenes [6,7], meroterpenes [2], etc.…”

Development and Characterization of Monoclonal Antibodies for the Mycotoxin Citreoviridin

“…A mechanism that involves the exacerbation or causation of thiamine deficiency would be consistent with the involvement of CTV in Shoshin-kakke. Recently, the toxicokinetics of CTV was determined in swine [11]. Results suggested that following oral exposure, CTV was readily absorbed by swine, and slowly metabolized, with a half-life of 21 h [11].…”

“…Recently, the toxicokinetics of CTV was determined in swine [11]. Results suggested that following oral exposure, CTV was readily absorbed by swine, and slowly metabolized, with a half-life of 21 h [11].…”