Oral cocaine produces dose-related hepatotoxicity in male mice

Labib, Ramez; Turkall, Rita M.; Abdel‐Rahman, Mohamed S.

doi:10.1016/s0378-4274(01)00412-x

Cited by 29 publications

(33 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This results in a disruption in the hepatic GSH and cellular reducing equivalents (NADPH), and impairment of antioxidant enzymes including GPx and CAT (Devi and Chan 1996;DiezFernandez et al 1999;Zarazoga et al 2000;Labib, Turkall, and Abdel-Rahman 2001). This injury can be reversed by inhibition of cocaine oxidative metabolism or by antioxidant pretreatment.…”

Section: Figure 10mentioning

confidence: 99%

Endotoxin Potentiates Cocaine-Mediated Hepatotoxicity by Nitric Oxide and Reactive Oxygen Species

2003

Self Cite

View full text Add to dashboard Cite

Exposure to small, noninjurious doses of the inflammagen, bacterial endotoxin (lipopolysaccharide, LPS) augments the toxicity of certain hepatotoxicants, including cocaine. The mechanism of this interaction has not been clearly elucidated, but it seems that aspects of the inflammatory response initiated by exposure to LPS may be responsible. In particular, this study examined the role of Kupffer cells and the modulating effects of nitric oxide (NO) and reactive oxygen species (ROS) on the LPS potentiation of cocaine-mediated hepatotoxicity (CMH). Mice were administered oral cocaine hydrochloride for 5 consecutive days at a dose of 20 mg/kg with and without 12 x 10(6) EU LPS/kg given intraperitoneally (IP) 4 hours after the last cocaine injection. Pretreatment regimens consisted of administration of 300 mg/kg, IP, of aminoguanidine (AM) or 1,3-dimethylthiourea (DMU) at 1 hour or 15 minutes, respectively, before each cocaine administration. In another group, mice were pretreated with saline using the same cocaine and LPS treatment protocol, but received a single pretreatment of 7 mg gadolinium chloride (GdCl(3))/kg intravenously (IV), or sterile saline 24 hours prior to the LPS administration. The GdCl(3) (Kupffer cell inhibitor) pretreatment inhibited the LPS potentiation of CMH, but did not reverse the effects of cocaine alone. On the other hand, AM (NO synthase inhibitor), decreased the synthesis of NO as observed by the decrease in the plasma nitrate/nitrite level and completely reversed the hepatotoxic effects of cocaine and LPS alone and in combination. Moreover, DMU (hydroxyl free radical scavenger) ameliorated the effects of cocaine and significantly reduced the hepatotoxicity observed with the cocaine and LPS administration. These data suggest that cocaine sensitizes the liver and subsequent activation of Kupffer cells by LPS leads to the formation of increased levels of NO, which can promote oxidant stress and thus provide an environment favoring the generation of more reactive species such as the hydroxyl free radical.

show abstract

Section: Figure 10mentioning

confidence: 99%

Endotoxin Potentiates Cocaine-Mediated Hepatotoxicity by Nitric Oxide and Reactive Oxygen Species

2003

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cocaine administration decreased the blood concentration of the main cellular antioxidant GSH (Visalli et al 2005; Labib et al 2001, 2002), and the effect was suggested to be a result of the increased production of ROS by this drug of abuse (Dietrich et al 2005; Kovacic 2005; Visalli et al 2005). In contrast, in the liver, cocaine increased the GSH concentration (Labib et al 2001, 2002), which may be explained by compensatory de novo synthesis of this antioxidant in hepatocytes (Wiener and Reith 1990; Mehanny and Abdel-Rahman 1991).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, in the liver, cocaine increased the GSH concentration (Labib et al 2001, 2002), which may be explained by compensatory de novo synthesis of this antioxidant in hepatocytes (Wiener and Reith 1990; Mehanny and Abdel-Rahman 1991). Interestingly, in brain, the cocaine treatment induced a decline of GSH content in the hippocampus (Muriach et al 2010), but no alterations were observed in the prefrontal cortex and striatum (Wiener and Reith 1990).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

et al. 2013

View full text Add to dashboard Cite

The aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration.

show abstract

“…En caso de una ingesta puntual en el curso de la abstinencia, se exigirán 6 meses de abstinencia total desde el momento de la recaída. Si hay un segundo consumo, se excluirá al paciente [8][9][10][11][12] .…”

Section: Article In Pressunclassified

Guía clínica de evaluación de pacientes con conductas adictivas para trasplante hepático

Lligoña

Freixa

Bataller

et al. 2009

Gastroenterología y Hepatología

View full text Add to dashboard Cite

Oral cocaine produces dose-related hepatotoxicity in male mice

Cited by 29 publications

References 37 publications

Endotoxin Potentiates Cocaine-Mediated Hepatotoxicity by Nitric Oxide and Reactive Oxygen Species

Endotoxin Potentiates Cocaine-Mediated Hepatotoxicity by Nitric Oxide and Reactive Oxygen Species

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Guía clínica de evaluación de pacientes con conductas adictivas para trasplante hepático

Contact Info

Product

Resources

About