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Platelets prevent the development of monocrotaline-induced liver injury in mice.
- Source :
-
Toxicology letters [Toxicol Lett] 2020 Dec 15; Vol. 335, pp. 71-81. Date of Electronic Publication: 2020 Oct 22. - Publication Year :
- 2020
-
Abstract
- Destruction of liver sinusoidal endothelial cells (LSECs) is an initial event in sinusoidal obstruction syndrome (SOS) that leads to accumulation of platelets in the liver. Herein, we explored the role of platelets during progression of experimental SOS induced by monocrotaline (MCT) in mice. Depletion of platelets using an anti-CD41 antibody or anti-thrombocyte serum exacerbated MCT-induced liver injury in C57BL/6 mice, as indicated by an increase in the alanine transaminase (ALT) level, which was associated with hemorrhagic necrosis. Thrombocytosis induced by thrombopoietin (TPO) or the TPO receptor agonist romiplostim (ROM) attenuated MCT-induced liver injury, as evidenced by lower levels of ALT and mRNA encoding matrix metalloproteinase (MMP) 9, and higher levels of mRNA encoding vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3. The level of activated hepatic platelets was higher in TPO- and ROM-treated mice than in saline-treated mice. Co-culture with a high number of platelets increased the viability of LSECs and their mRNA levels of CD31, VEGFR2, and VEGFR3, and decreased their mRNA level of MMP9. The level of VEGF-A was increased in the culture medium of LSECs co-cultured with platelets. These results indicate that platelets attenuate MCT-induced liver injury by minimizing damage to LSECs.<br />Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose.<br /> (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Blood Platelets cytology
Cell Survival drug effects
Chemical and Drug Induced Liver Injury, Chronic prevention & control
Coculture Techniques
Endothelial Cells drug effects
Endothelial Cells pathology
Hepatic Veno-Occlusive Disease prevention & control
Liver Function Tests
Male
Mice, Inbred C57BL
Platelet Count
Receptors, Fc
Receptors, Thrombopoietin agonists
Recombinant Fusion Proteins pharmacology
Thrombocytosis chemically induced
Thrombopoietin pharmacology
Blood Platelets drug effects
Chemical and Drug Induced Liver Injury, Chronic blood
Hepatic Veno-Occlusive Disease blood
Hepatic Veno-Occlusive Disease chemically induced
Monocrotaline toxicity
Thrombocytosis blood
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 335
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 33122006
- Full Text :
- https://doi.org/10.1016/j.toxlet.2020.10.007