Palytoxin toxicity after acute oral administration in mice.

Toxicol Lett

Department of Materials and Natural Resources, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy.

Published: December 2009

The acute oral toxicity of palytoxin (PLTX), a highly toxic compound associated with seafood intoxication in tropical and subtropical areas, was investigated in mice. After gavage administration (300-1697 microg/kg) to groups of five female CD-1 mice, signs of toxicity and lethality were recorded for 24 h. The LD(50) was 767 microg/kg (95% confidence limits: 549-1039 microg/kg) and the main symptoms observed were scratching, jumping, respiratory distress and paralysis. Hematoclinical analyses showed increased levels of creatine phosphokinase and lactate dehydrogenase at doses of 600 microg/kg and above, and aspartate transaminase at 848 microg/kg and above. Histological analysis revealed acute inflammation of the forestomach in mice surviving up to 24h after administration (424-1200 microg/kg). Other histological alterations were observed in the liver and pancreas, while cardiac and skeletal muscle cells revealed only ultrastructural alterations visible by transmission electron microscopy. Ultrastructural and hematoclinical findings suggest an involvement of skeletal and/or cardiac muscle as targets of PLTX, according to the observed human symptoms. A NOEL of 300 microg/kg can be estimated from this acute oral toxicity study.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2009.09.009DOI Listing

Publication Analysis

Top Keywords

acute oral
12
oral toxicity
8
microg/kg histological
8
microg/kg
7
palytoxin toxicity
4
acute
4
toxicity acute
4
oral administration
4
mice
4
administration mice
4

Similar Publications

Could New Palm-Free Structured Lipids Mitigate Postprandial Hyperlipidemia and Inflammation Induced by High-Fat Meals in Swiss Mice?

J Am Nutr Assoc

January 2025

Department of Food Science and Nutrition, Faculty of Food Engineering, Universidade Estadual de Campinas - UNICAMP, Campinas, SP, Brazil.

A high-fat meal can cause postprandial hyperlipemia, initiating an acute inflammatory response. New structured lipids (SLs) free from trans and palm fatty acids are emerging as food structurants. We evaluated the postprandial response and inflammatory profiles in Swiss mice after oral administration of SLs in high-fat meals.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Axsome Therapeutics, New York, NY, USA.

Background: Patients with Alzheimer's disease (AD) often experience burdensome neuropsychiatric symptoms, including agitation which occurs in both home and long-term care (LTC) facilities, and is associated with substantial increases in caregiver burden and LTC placements. AXS-05 (45-mg dextromethorphan/105-mg bupropion), a novel, oral NMDA receptor antagonist and sigma-1 receptor agonist, approved by the FDA for major depressive disorder, is being investigated for treatment of AD agitation (ADA). AXS-05 has been evaluated in 2 randomized, double-blind studies: Phase 2 ADVANCE-1 (NCT03226522); Phase 3 ACCORD (NCT04797715).

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Oligomerix, Inc., Bronx, NY, USA.

Background: OLX-07010 is an oral small molecule inhibitor of tau self-association that prevented the accumulation of tau aggregates in the htau mouse model expressing wild type human CNS tau isoforms and in P301L tau JNPL3 mice using chronic treatment by administration in diet (Davidowitz et al., 2020, PMID: 31771053; 2023 PMID:37556474). A therapeutic study of JNPL3 mice with chronic treatment from 7-12 months of age inhibited the progression of tau aggregation and improved motor coordination.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

UCSD, San Diego, CA, USA.

Cerebral beta-amyloid accumulation is the key initiator of Alzheimer's disease (AD) pathology. Most familial early-onset AD mutations in the APP, PSEN1/2 genes increase the ratio of Abeta42:Abeta40, which drives beta-amyloid accumulation in the brain. In 2001, the late Steve Wagner, Maria Kounnas, and I directed an agnostic high-throughput screen for compounds that would reverse the Abeta42:Abeta40, ratio, and discovered the first non-NSAID (second generation) gamma secretase modulators (GSM) at TorreyPines Therapeutics.

View Article and Find Full Text PDF

The modern use of hydroxyurea for children with sickle cell anemia.

Haematologica

January 2025

Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati OH; University of Cincinnati College of Medicine, Cincinnati OH; Global Health Center, Cincinnati Children's Hospital Medical Center, Cincinnati OH.

Over the past 40 years, the introduction and refinement of hydroxyurea therapy has led to remarkable progress for the care of individuals with sickle cell anemia (SCA). From initial small proof-of-principle studies to multi-center Phase 3 controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan. Elevated fetal hemoglobin (HbF) serves as the most important treatment response, as HbF delays sickle hemoglobin polymerization and reduces erythrocyte sickling.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!