Cocaine Toxicity and Hepatic Oxidative Stress

Vitcheva, Vessela

doi:10.2174/092986712803988929

Cited by 31 publications

(21 citation statements)

References 37 publications

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“…Furthermore, several lines of evidence indicate that excessive OS with increased free radical generation, impairment of mitochondrial respiration, and intense inflammatory reaction plays a crucial role in cocaine-induced hepatotoxicity. OS is associated with the dysregulation of signaling pathways modulating cell death and survival, which leads to necrosis and apoptosis of hepatocytes [ 6 ]. Although previous studies have yielded mechanistic information on cocaine-induced hepatotoxicity, the current understanding on this toxic event remains insufficient [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is well described that the prevention of OS generation might have therapeutic advantages in several diseases [ 6 , 10 , 11 ]; therefore, the investigation of putative new compounds with antioxidant properties might be promising. The herb Cannabis sativa (“marijuana,” “hemp”) has been known for centuries due to its abuse-related effects and possible therapeutic uses, including the treatment of inflammation, diabetes, cancer, affective or neurodegenerative diseases, and epilepsy-related disorders.…”

Section: Introductionmentioning

confidence: 99%

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Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

Vilela

Gomides

David

et al. 2015

Mediators of Inflammation

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

Vilela

Gomides

David

et al. 2015

Mediators of Inflammation

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“…For example, MDMA (ecstasy) and cocaine can cause chronic hepatitis and liver fibrosis (Payance, Scotto, Perarnau, de Muret, & Bacq, 2013). In addition, cocaine use can induce severe hepatotoxicity (Vitcheva, 2012) and cannabis use exacerbates HCV-associated liver disease (Hezode et al, 2005; Ishida et al, 2008). However, few studies to date have reported the use of addictive drugs in people with HIV-HCV co-infection relative to persons with HIV mono-infection.…”

Section: Introductionmentioning

confidence: 99%

Continued Substance Use Among People Living With HIV–Hepatitis-C Co-Infection and Receiving Antiretroviral Therapy

Kalichman

Washington

Kegler

et al. 2015

Substance Use & Misuse

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Background Co-infection with HIV and Hepatitis-C virus (HCV) poses a significant threat to personal and public health. Substance use among co-infected persons leads to increased morbidity and mortality. The purpose of this study is to examine the continued substance use of people living with HIV-HCV co-infection and receiving antiretroviral therapy (ART). Methods Individuals living with HIV infection in Atlanta, GA and currently receiving ART (N = 678) completed audio-computer assisted self-interviews for demographic, health, and behavior characteristics; unannounced pill counts to assess ART adherence over one-month; finger-stick blood specimens collected for HCV antibody testing and urine specimens for drug use screening; and obtained HIV viral load and CD4 cell counts from their medical provider. We performed cross-sectional analyses of behavioral and biological markers of health, health behaviors, and substance use. Results Among participants 131 (19%) were HIV-HCV co-infected; 53% of HIV-mono-infected and 60% of HIV-HCV co-infected participants tested positive for use of at least one non-alcohol drug; THC and cocaine were most prevalent. HIV-HCV co-infected individuals were older, with no other significant differences. Within the HIV-HCV co-infected participants, drug users (N = 87) did not differ from non-drug users (N= 53) in terms of ART adherence. However, drug users were significantly more likely to have uncontrolled HIV (17%) compared to those who did not test drug positive (4%). Conclusions Substance use is prevalent in persons with HIV-HCV co-infection and may interfere with ART. Research with a larger more representative sample is needed to replicate and confirm these results.

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“…Está descrito que en la hepatotoxicidad por cocaína, la peroxidación de lípidos inducida por estrés oxidativo se encuentra relacionada con las hormonas sexuales, especialmente la testosterona, con menor daño en mujeres con ovarios intactos 19,20 . Sin embargo, nuestros hallazgos se contraponen a estas observaciones, probablemente debido al menor número de mujeres, por lo que no podemos aseverar que esté relacionado con el efecto de hormonas sexuales como ha sido descrito para otras alteraciones.…”

Section: Discussionunclassified