Toxicon 51 (2008) 1225–1235 Ultrastructural damage to heart tissue from repeated oral exposure to yessotoxin resolves in 3 months $ A. Tubaro a,Ã , A. Giangaspero a , M. Ardizzone b , M.R. Soranzo c , F. Vita c , T. Yasumoto d , J.M. Maucher e , J.S. Ramsdell e , S. Sosa a a Department of Materials and Natural Resources, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy b Istituto di Ricerche Biomediche ‘‘Antoine Marxer’’ RBM SpA, Via Ribes 1, 10010 Colleretto Giacosa (TO), Italy 1 c Department of Physiology and Pathology, University of Trieste, Via Fleming 22, 34127 Trieste, Italy d Tama Laboratory, Japan Food Research Laboratories, 6-11-10 Nagayama, Tama, 206-0025 Tokyo, Japan e Marine Biotoxins Program, National Oceanic and Atmospheric Administration-National Ocean Service, 219 Fort Johnson Road, Charleston, SC, USA Received 11 February 2008; accepted 12 February 2008 Available online 26 February 2008 Abstract Yessotoxin (YTX), an algal toxin contaminating edible shellfish, was previously shown to induce ultrastructural changes in some cardiac muscle cells of mice after acute (1 and 2 mg/kg) or daily repeated oral exposure (1 and 2 mg/kg/day, for 7 days). Therefore, the temporal evolution of the ultrastructural myocardial alterations and the development of other signs of toxicity induced by a repeated daily oral administration of YTX (1 mg/kg/day, for 7 days) to mice were evaluated within 3 months after the treatment. Symptoms, food consumption, body weight, gross pathology and histopathology of the main organs and tissues were observed, and plasma levels of transaminases, lactate dehydrogenase, creatinine and creatinine phosphokinase were measured. Heart, liver, kidneys and cerebellum were also analysed by transmission electron microscopy. In addition, the blood concentration of YTX was determined by a direct enzyme linked immunosorbent assay (ELISA) 24 h after the last toxin administration. No mortality or other treatment-related changes, including histological or hematoclinical parameters, were recorded in mice administered with YTX. Similarly, electron microscopy did not reveal any ultrastructural alteration in the liver, kidneys, and cerebellum associated with YTX treatment. In contrast, changes in cardiac muscle cells near to the capillaries (clusters of rounded mitochondria and disorganization of myofibrils) were observed 24 h after the treatment. These changes were also noted 30 days after the toxin administration, while after 90 days no differences in cardiac muscle cells ARTICLE IN PRESS www.elsevier.com/locate/toxicon 0041-0101/$ - see front matter r 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.toxicon.2008.02.011 $ Ethical statement: As corresponding author of the manuscript entitled ‘‘Ultrastructural damage to heart tissue from repeated oral exposure to yessotoxin resolves in 3 months’’ that was accepted for publication in Toxicon. I declare that the material has not been published in whole or in part elsewhere; the paper is not currently being considered for publication elsewhere; all authors have been personally and actively involved in substantive work leading to the paper, and will hold themselves jointly and individually responsible for its content. Ã Corresponding author. Tel.: +39 040 558 7910; fax: +39 040 558 3215. E-mail address: tubaro@units.it (A. Tubaro). 1 Company under the direction and coordination of Merck Serono S.A.-Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.