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. 2019 Mar 19;11(3):169.
doi: 10.3390/toxins11030169.

Bioaccumulation and Distribution of Indospicine and Its Foregut Metabolites in Camels Fed Indigofera spicata

Gabriele Netzel  1 , Eddie T T Tan  2   3 , Mukan Yin  4 , Cindy Giles  5 , Ken W L Yong  6 , Rafat Al Jassim  7 , Mary T Fletcher  8
Affiliations

Bioaccumulation and Distribution of Indospicine and Its Foregut Metabolites in Camels Fed Indigofera spicata

Gabriele Netzel et al. Toxins (Basel). .

Abstract

In vitro experiments have demonstrated that camel foregut-fluid has the capacity to metabolize indospicine, a natural toxin which causes hepatotoxicosis, but such metabolism is in competition with absorption and outflow of indospicine from the different segments of the digestive system. Six young camels were fed Indigofera spicata (337 µg indospicine/kg BW/day) for 32 days, at which time three camels were euthanized. The remaining camels were monitored for a further 100 days after cessation of this indospicine diet. In a retrospective investigation, relative levels of indospicine foregut-metabolism products were examined by UHPLC-MS/MS in plasma, collected during both accumulation and depletion stages of this experiment. The metabolite 2-aminopimelamic acid could be detected at low levels in almost all plasma samples, whereas 2-aminopimelic acid could not be detected. In the euthanized camels, 2-aminopimelamic acid could be found in all tissues except muscle, whereas 2-aminopimelic acid was only found in the kidney, pancreas, and liver tissues. The clearance rate for these metabolites was considerably greater than for indospicine, which was still present in plasma of the remaining camels 100 days after cessation of Indigofera consumption.

Keywords: 2-aminopimelamic acid; 2-aminopimelic acid; camel; food safety; foregut metabolites; in vivo; indospicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of indospicine (1) and its metabolites 2-aminopimelamic acid (2) and 2-aminopimelic acid (3), together with D3-l-indospicine (4) which is used as an internal standard in LC-MS/MS analysis.
Figure 2
Figure 2
Mean concentrations (mg/kg FW) of indospicine, 2-aminopimelamic acid, and 2-aminopimelic acid for camels 1–3 necropsy tissues (heart, spleen, pancreas, muscle, liver and kidney) after 32-day feeding period.
Figure 3
Figure 3
Comparison of indospicine and 2-aminopimelic acid concentrations in plasma (mean ± SD) during the first 32 days (n = 6) of the treatment and after cessation of Indigofera spicata feeding (n = 3). Camels 1–3 were autopsied at day 33.
Figure 4
Figure 4
Individual 2-aminopimelamic acid concentrations of plasma during the first 32 days (n = 6) of the treatment and after cessation of Indigofera spicata feeding (n = 3). Camels 1–3 were autopsied at day 33.
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