Impact of Microcystin-LR on Liver Function Varies by Dose and Sex in Mice
Autor: | Mark A. Morse, Shambhunath Choudhary, Jiyoung Lee, Randall J. Ruch, Igor Mrdjen, Christopher M. Weghorst, Thomas J. Knobloch |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Necrosis Microcystins Bilirubin Health Toxicology and Mutagenesis Physiology lcsh:Medicine Microcystin-LR Cell Communication 010501 environmental sciences Toxicology 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Mice liver health medicine Animals 0105 earth and related environmental sciences Sex Characteristics cyanotoxin lcsh:R Gap Junctions Cyanotoxin harmful algal blooms 030104 developmental biology female and male chemistry Liver Toxicity ingestion Alkaline phosphatase Histopathology Female Marine Toxins Liver function medicine.symptom acute exposure |
Zdroj: | Toxins Volume 10 Issue 11 Toxins, Vol 10, Iss 11, p 435 (2018) |
ISSN: | 2072-6651 |
Popis: | Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, and death in extreme circumstances. The goal of this study was to provide an accurate and comprehensive description of MC-LRs impacts on liver pathology, clinical chemistry, and gap junction intercellular communication (GJIC) in CD-1 male and female mice. Mice were exposed to 0, 3000, and 5000/4000 µ g/kg/day MC-LR, daily for 7 days, and were necropsied on Day 8. Blood samples for clinical chemistry analysis were processed to serum, while liver sections were fixed for histopathology or evaluated for GJIC using fluorescent cut-load dye. Results show a dose-dependent relationship with MC-LR exposure and hepatocellular hypertrophy, degradation, and necrosis. Clinical chemistry parameters alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and cholesterol increased significantly in MC-LR exposed mice. Clinical chemistry parameter analysis showed significantly increased susceptibility to MC-LR in females compared to males. Changes in GJIC were not noted, but localization of hepatotoxicity near the central veins and midlobular areas was seen. Future toxicity studies involving MCs should consider response differences across sexes, differing MC congeners, and combinatorial exposures involving other cyanotoxins. |
Databáze: | OpenAIRE |
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