The Course of Toxicity in the Pregnant Mouse After Exposure to the Cyanobacterial Toxin Cylindrospermopsin: Clinical Effects, Serum Chemistries, Hematology, and Histopathology

Abstract

Cylindrospermopsin (CYN) is a toxin produced by a variety of fresh-water cyanobacterial species worldwide and induces significant adverse effects in both livestock and humans. This study investigated the course of CYN-induced toxicity in pregnant mice exposed daily during either the period of major organogenesis (gestation days [GD] 8–12) or fetal growth (GD13–17). Endpoints include clinical signs of toxicity, serum analyses to evaluate hepatic and renal function, histopathology of liver and kidney, and hematology. Study animals were administered 50 μg/kg CYN once daily by ip route and euthanized 24 h after 1, 2, 3, 4, or 5 consecutive doses, or 6 or 13 d after the dosing period. The course of the CYN-induced effects was determined at all euthanasia times for the endpoints just outlined. Results indicated that CYN is a toxin, producing lethality in dams during the early part of gestation, significant weight loss, and bleeding in the gastrointestinal tract, tail tip, and peri-orbital tissues. Effects also included alterations in serum markers for liver function, histopathological changes in liver and kidney tissues, electrolyte abnormalities, leukocytosis, and posttreatment thrombocytopenia and reticulocytosis. The onset of symptoms was rapid, producing reductions in weight gain in GD8–12 animals, bleeding in the vaginal area in GD13–17 animals, and significant increases in sorbitol dehydrogenase (SDH) in both groups after a single dose. Although the GD8–12 dams displayed a 50% lethality, in GD13–17 animals only a single death occurred. Alterations seen in hepatic and renal function or histopathology do not appear to be of sufficient severity to produce death. Evidence indicates that bleeding may play a critical role in the onset of symptoms and eventually, in the observed lethality.

ACKNOWLEDGwMENTS

We are grateful to Eli Ney of NIEHS for her assistance with the photomicrograph.

FUNDING

This research was supported [in part] by the Division of the National Toxicology Program of the NIH, National Institute of Environmental Health Sciences. The information in this document has been funded by the U.S. Environmental Protection Agency. It has been subject to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH); however, the statements, opinions, or conclusions contained herein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the U.S. Government.