scholarly journals Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Luciano Rezende Vilela ◽  
Lindisley Ferreira Gomides ◽  
Bruna Araújo David ◽  
Maísa Mota Antunes ◽  
Ariane Barros Diniz ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Acute Liver Injury ◽  
Endocannabinoid System ◽  
Protective Role ◽  
Acute Liver Damage ◽  
Protective Actions ◽  
Cocaine Toxicity ◽  
Hepatotoxic Drug

Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

A protective role of IL-22BP in acute liver injury

2017 ◽  
Vol 66 (1) ◽  
pp. S333-S334
Author(s):  
D. Kleinschmidt ◽  
A.D. Giannou ◽  
J. Kempski ◽  
B. Steglich ◽  
F.J. Huber ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Protective Role

scholarly journals Protective Role of Genistein in Acute Liver Damage Induced by Carbon Tetrachloride

2007 ◽  
Vol 2007 ◽  
pp. 1-6 ◽  
Author(s):  
Nalan Kuzu ◽  
Kerem Metin ◽  
Adile Ferda Dagli ◽  
Fatih Akdemir ◽  
Cemal Orhan ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Damage ◽  
Protective Role ◽  
Acute Liver Damage

scholarly journals Histone methyltransferase G9a protects against acute liver injury through GSTP1

2019 ◽  
Vol 27 (4) ◽  
pp. 1243-1258 ◽  
Author(s):  
Yu Zhang ◽  
Weili Xue ◽  
Wenquan Zhang ◽  
Yangmian Yuan ◽  
Xiuqin Zhu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Damage ◽  
Acute Liver Injury ◽  
Epigenetic Modification ◽  
Histone Methyltransferase ◽  
Methyltransferase Activity ◽  
Detoxifying Enzymes ◽  
Apap Overdose ◽  
Deficient Mice

Abstract Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS- or APAP overdose-induced acute liver injury. Under d-galactosamine sensitization, liver-specific G9a-deficient mice (L-G9a−/−) exhibited 100% mortality after LPS injection, while the control and L-G9a+/− littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a−/− mice displayed more severe liver injury. Mechanistically, ablation of G9a inhibited H3K9me1 levels at the promoters of Gstp1/2, two liver detoxifying enzymes, and consequently suppressed their transcription. Notably, treating L-G9a−/− mice with recombinant mouse GSTP1 reversed the LPS- or APAP overdose-induced liver damage. Taken together, we identify a novel beneficial role of G9a-GSTP1 axis in protecting against acute liver injury.

scholarly journals Acute liver injury following acetaminophen administration does not activate atrophic pathways in the mouse diaphragm

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. S. Bruells ◽  
P. Duschner ◽  
G. Marx ◽  
G. Gayan-Ramirez ◽  
N. Frank ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Liver Injury ◽  
Liver Damage ◽  
Acute Liver Injury ◽  
Serum Levels ◽  
Acute Liver Damage ◽  
Markers Of Inflammation ◽  
Amino Phenol ◽  
And Oxidative Stress

AbstractN-acetyl-para-amino phenol (APAP, usually named paracetamol), which is commonly used for its analgesic and antipyretic properties may lead to hepatotoxicity and acute liver damage in case of overdoses. Released cytokines and oxidative stress following acute liver damage may affect other organs’ function notably the diaphragm, which is particularly sensitive to oxidative stress and circulating cytokines. We addressed this issue in a mouse model of acute liver injury induced by administration of APAP. C57BL/6J mice (each n = 8) were treated with N-acetyl-para-amino phenol (APAP) to induce acute drug caused liver injury and sacrificed 12 or 24 h afterwards. An untreated group served as controls. Key markers of inflammation, proteolysis, autophagy and oxidative stress were measured in diaphragm samples. In APAP treated animals, liver damage was proven by the enhanced serum levels of alanine aminotransferase and aspartate aminotransferase. In the diaphragm, besides a significant increase in IL 6 and lipid peroxidation, no changes were observed in key markers of the proteolytic, and autophagy signaling pathways, other inflammatory markers and fiber dimensions. The first 24 h of acute liver damage did not impair diaphragm atrophic pathways although it slightly enhanced IL-6 and lipid peroxidation. Whether longer exposure might affect the diaphragm needs to be addressed in future experiments.

scholarly journals Novel Protective Role of Nicotinamide Phosphoribosyltransferase in Acetaminophen-Induced Acute Liver Injury in Mice

2018 ◽  
Vol 188 (7) ◽  
pp. 1640-1652 ◽  
Author(s):  
Li Q. Zhang ◽  
Marianne Nsumu ◽  
Peixin Huang ◽  
Daniel P. Heruth ◽  
Sean M. Riordan ◽  
...  
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Protective Role ◽  
Nicotinamide Phosphoribosyltransferase
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