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New Insights Into Dietary Toxin Metabolism: Diversity in the Ability of the Natricine Snake Rhabdophis tigrinus to Convert Toad-Derived Bufadienolides

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Abstract

The Japanese natricine snake Rhabdophis tigrinus sequesters cardiotonic steroids, bufadienolides (BDs), from ingested toads in the nuchal glands as defensive toxins. A previous study showed that R. tigrinus in captivity converts dietary BDs when it sequesters them. However, it is unknown whether the dietary BDs are actually converted and the modified products accumulated under natural conditions. It is also unknown to what extent the BD profile of ingested toads is reflected in that of the snake. We collected 123 snakes from throughout Japan, analyzed their BD profiles by liquid chromatography/mass spectrometry, and identified 15 BDs from R. tigrinus by nuclear magnetic resonance analyses. We also compared their BD profiles using hierarchical cluster analysis (HCA). HCA exhibited two main clusters associated with their collection locations: eastern and western regions of the Japanese main islands. These results, coupled with previous findings on the BDs of Japanese toads, suggest that 1) R. tigrinus converts toad-derived BDs into other compounds under natural conditions; 2) there are both universal and regionally-specific conversions of dietary BDs by R. tigrinus; and 3) geographic variation in toad BD profiles is partially reflected in the variation of snake BD profiles.

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Acknowledgements

We thank K. Eto, S. Fujii, K. Fujishima, M. Fukuda, I. Fukuyama, R. Fukuyama, K. Hamanaka, S. Ichihara, K. Kanda, T. Kodama, J. Marunouchi, T. Matsuki, H. Moriguchi, E. Moriki, K. Nishikawa, K. Niwa, T. Okamoto, M. Tagawa, S. Tanabe, S. Tsukamoto, S. Yoden, and the staff of Shizuoka Prefectural Forest Park for collecting snakes. We thank R. Ujiie and T. Yoshida for their keen insights during discussions.

Funding

This research was supported by grants from Japan–China Joint Research Project (2014–2016) between the Japan Society for the Promotion of Science (JSPS) and National Natural Science Foundation of China (NSFC, 31411140033) and JSPS KAKENHI Grant Numbers JP26440213, JP17H03719, and JP18KK0205. Additional funding was provided by Utah State University.

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Contributions

Conceptualization: Inoue T, Nakata R, Savitzky AH, Yoshinaga N, Mori A, Mori N.

Data curation: Inoue T, Nakata R, Savitzky AH, Yoshinaga N, Mori A, Mori N.

Formal analysis: Inoue T, Nakata R, Yoshinaga N, Mori N.

Funding acquisition: Mori A.

Investigation: Inoue T, Nakata R, Savitzky AH, Mori A, Mori N.

Methodology: Inoue T, Nakata R, Yoshinaga N, Mori A, Mori N.

Project administration: Inoue T, Nakata R, Mori A, Mori N.

Resources: Inoue T, Mori A.

Supervision: Inoue T, Nakata R, Savitzky AH, Yoshinaga N, Mori A, Mori N.

Validation: Inoue T, Nakata R, Yoshinaga N, Mori A, Mori N.

Visualization: Inoue T, Nakata R, Savitzky AH, Yoshinaga N, Mori A, Mori N.

Writing – original draft: Inoue T, Nakata R.

Writing – review & editing: Inoue T, Nakata R, Savitzky AH, Mori A, Mori N.

Corresponding author

Correspondence to Naoki Mori.

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The present study was carried out in compliance with the guidelines of the Animal Care and Use Committee of Kyoto University.

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All authors approved the manuscript to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Inoue, T., Nakata, R., Savitzky, A. et al. New Insights Into Dietary Toxin Metabolism: Diversity in the Ability of the Natricine Snake Rhabdophis tigrinus to Convert Toad-Derived Bufadienolides. J Chem Ecol 47, 915–925 (2021). https://doi.org/10.1007/s10886-021-01287-6

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  • DOI: https://doi.org/10.1007/s10886-021-01287-6

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