An Overview of the Anatomical Distribution of Tetrodotoxin in Animals

Abstract

Tetrodotoxin (TTX), a potent paralytic sodium channel blocker, is an intriguing marine toxin. Widely distributed in nature, TTX has attracted attention in various scientific fields, from biomedical studies to environmental safety concerns. Despite a long history of studies, many issues concerning the biosynthesis, origin, and spread of TTX in animals and ecosystems remain. This review aims to summarize the current knowledge on TTX circulation inside TTX-bearing animal bodies. We focus on the advances in TTX detection at the cellular and subcellular levels, providing an expanded picture of intra-organismal TTX migration mechanisms. We believe that this review will help address the gaps in the understanding of the biological function of TTX and facilitate the development of further studies involving TTX-bearing animals.

Keywords: TTX; TTX-bearing animals; biotoxin; tetrodotoxin.

Figure 1

Schematic illustration of the levels and intra-organismal distribution of tetrodotoxin (TTX) in the adult pufferfish (family Tetraodontidae). Red color on the insets indicates TTX-positive cells. I—Skin with dermal gland (dg). II—Skin with singly scattered succiform cells (sc). III—Oocytes on different maturation stages: a—immature oocyte, b—newly mature oocyte, c—mature oocyte. IV—Intestinal epithelium (iep) and sac-like tissue (slt) outside the serous membrane (sm). V—Liver with hepatocytes (hc). Abbreviations: ec, epithelial cell; bc, basal cell; dg, dermal gland; dgc, dermal gland cell; f-TTX, free TTX; sc, succiform cell; n, nuclei; yg, yolk granules; iep, intestinal epithelium; slt, sac-like tissue; sm, serous membrane; hc, hepatocyte.

Figure 2

Schematic illustration of the levels and intra-organismal distribution of tetrodotoxin (TTX) in the adult newt (family Salamandridae). Red color on the insets indicates TTX-positive cells. I—Skin with mature granular (gg) and mixed (mg) glands. Abbreviations: ec, epithelial cell; gc, glandular cell; gg, mature granular gland; mg, mature mixed gland; f-TTX, free TTX.

Figure 3

Schematic illustration of the levels and intra-organismal distribution of tetrodotoxin (TTX) in molluscs. Red color on the insets indicates TTX-positive cells. (A)—Blue-ringed octopus (genus Hapalochlaena). I—Posterior salivary gland with glandular cells (gc). (B)—Marine gastropod (genus Pleurobranchaea). I—The epidermis of the mantle. II—Digestive gland with glandular cells (gc). III—Oocytes (oc) surrounded by follicles (fc). (C)—Marine bivalve mollusc (genus Paphies). I—Siphon with TTX-positive cells located under the epithelium (ep). Gills (II), intestine (III), and labial palp (IV) showing epithelium (ep). Abbreviations: gc, glandular cells; bm, basement membrane; ec, epithelial cells; nmc, neutral mucin cells; oc, oocytes; fc, follicles; ep, epithelium.

Figure 4

Schematic illustration of the levels and intra-organismal distribution of tetrodotoxin (TTX) in the marine ribbon worm (genus Cephalothrix). Red color on the insets indicates TTX-positive cells. I—Glandular epithelium of proboscis. II—Intestinal epithelium. III—Protonephridium (pn) associated with the blood vessel (bv). IV—Cephalic gland. V—Integument. VI—Oocytes. Abbreviations: pgs, proboscidial gland cell; sc, supportive cell; ent, enterocyte; igs, intestinal glandular cell; bv, blood vessel; pn, protonephridium; tc, terminal cell; cc, ciliary cell; cgc, cephalic gland cell; f-TTX, free TTX; egc, epidermal gland cells; yg, yolk granules.

Figure 5

Schematic illustration of the levels and intra-organismal distribution of tetrodotoxin (TTX) in the marine flatworm (order Polycladida). Red color on the insets indicates TTX-positive cells. I—Oocytes. II—Pharynx showing epithelial cells (ep) and parenchyma (prh).

Figure 6

Schematic illustration of tetrodotoxin (TTX) migration in TTX-bearing animals.