Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine
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 l...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/523418 |
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| author | Luciano Rezende Vilela Lindisley Ferreira Gomides Bruna Araújo David Maísa Mota Antunes Ariane Barros Diniz Fabrício de Araújo Moreira Gustavo Batista Menezes |
| author_facet | Luciano Rezende Vilela Lindisley Ferreira Gomides Bruna Araújo David Maísa Mota Antunes Ariane Barros Diniz Fabrício de Araújo Moreira Gustavo Batista Menezes |
| author_sort | Luciano Rezende Vilela |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-041b0d7f8fc948cab76b3ccfed52e1af |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-041b0d7f8fc948cab76b3ccfed52e1af2025-02-03T01:24:21ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/523418523418Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by CocaineLuciano Rezende Vilela0Lindisley Ferreira Gomides1Bruna Araújo David2Maísa Mota Antunes3Ariane Barros Diniz4Fabrício de Araújo Moreira5Gustavo Batista Menezes6Laboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilLaboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilLaboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilLaboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilLaboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilDepartamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilLaboratório de Imunobiofotônica, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, BrazilCocaine 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.http://dx.doi.org/10.1155/2015/523418 |
| spellingShingle | Luciano Rezende Vilela Lindisley Ferreira Gomides Bruna Araújo David Maísa Mota Antunes Ariane Barros Diniz Fabrício de Araújo Moreira Gustavo Batista Menezes Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine Mediators of Inflammation |
| title | Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine |
| title_full | Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine |
| title_fullStr | Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine |
| title_full_unstemmed | Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine |
| title_short | Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine |
| title_sort | cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine |
| url | http://dx.doi.org/10.1155/2015/523418 |
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