The perturbation of hepatic glutathione by α2-adrenergic agonists

James, Robert C.; Roberts, Stephen M.; Harbison, Raymond D.

doi:10.1016/s0272-0590(83)80144-4

Cited by 19 publications

(1 citation statement)

References 20 publications

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“…The two-primary means of metabolism incorporate the esterases which are found in various tissues and organs and the oxidative pathway, performed by the liver. Cocaine can release epinephrine and norepinephrine into the circulating system which may give way to glutathione depletion in the liver (James et al, 1983;Register & Bartlett, 1954). Catecholamines seem to be elevated by some cocaine metabolites, which may lead to cocaine toxicity (Misra & Pontani, 1977;Williams et al, 1977) The primary cocaine metabolite, benzoylecgonine, was measured in the circulating plasma of rats throughout the entire study period.…”

Section: Cocaine Metabolism/plasma Metabolitesmentioning

confidence: 99%

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Gardner¹,

Luke

Wheatley

et al. 2015

International Journal of Measurement Technologies and Instrumentation Engineering

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The effects that chronic cocaine administration (CCA) have on craving, cocaine metabolite concentrations and cytochrome P450 3A4 isoenzyme (CYP450 3A4) activities in Sprague-Dawley rats following the administration of Salako Nutritional Supplements (SNS) were examined. Five groups of fifty rats were used to assess the effect of the SNS following CCA. Craving was analyzed for each rat using a Conditioned Place Preference protocol. Blood samples were obtained at regular intervals and used to measure cocaine plasma metabolite levels. CYP450 3A4 activity was determined in the liver. Administration of the SNS reduced craving of cocaine significantly, upon discontinuing cocaine in the rats. Blood plasma analysis showing higher benzoylecgonine equilibrium and the CYP450 3A4 levels demonstrated that the SNS possibly aided in the removal of the stored metabolites indicative of increased metabolism of cocaine, enhanced by the Supplements. Results indicate that the SNS formulation reduces craving caused by CCA by increasing the liver CYP450 3A4 activity, resulting in better plasma clearance.

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Section: Cocaine Metabolism/plasma Metabolitesmentioning

confidence: 99%

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Gardner¹,

Luke

Wheatley

et al. 2015

International Journal of Measurement Technologies and Instrumentation Engineering

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Metabolism-dependent hepatotoxicity of methimazole in mice depleted of glutathione

et al. 1999

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Methimazole (MMI) (>0.1 mmol kg−1, p.o.) given in combination withDL‐buthionine sulphoximine (BSO) (3 mmol kg−1, i.p., 1 h before MMI administration), an inhibitor of glutathione (GSH) synthesis, caused liver injury in mice. The injury was characterized by centrilobular necrosis of hepatocytes and an increase in serum alanine transaminase (ALT) activity. Methionazole (2 mmol kg−1) alone resulted in only a marginal increase in serum ALT activity, but produced no histopathological changes in the liver. Pretreatment with hepatic cytochrome P‐450 monooxygenase inhibitors—cobalt chloride, isosafrole, methoxsalen, metyrapone and piperonyl butoxide—prevented or tended to suppress the hepatotoxicity induced by MMI in combination with BSO. Treatment with N,N‐dimethylaniline and ethyl methyl sulphide, competitive substrates of flavin‐containing monooxygenases (FMO), also resulted in remarkable suppression of the hepatotoxicity caused by MMI in combination with BSO. These results suggest that MMI is activated by reactions mediated by both cytochrome P‐450 monooxygenases and FMO, and that the inadequate rates of detoxification of the resulting metabolite are responsible for the hepatotoxicity in GSH‐depleted mice. Copyright © 1999 John Wiley & Sons, Ltd.

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Hepatic biochemical changes as a result of acute cocaine administration in the mouse

Boyer

Petersen

1991

Hepatology

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The biochemical mechanism of cocaine hepatotoxicity is thought to involve enzymatic formation of reactive metabolites. The exact hepatocellular effects of these metabolites have yet to be established. This study was designed to monitor, in a time course after an acute cocaine dose, biochemical parameters that are important in cellular defense and homeostasis in vivo. The hepatic parameters measured were ATP as an indicator of cellular energetic status, reduced and oxidized glutathione, NADH and NADPH as measures of redox changes, and thiobarbituric acid-reactive products and microsomal conjugated dienes to determine the extent of lipid peroxidation. In addition, serum ALT levels were determined at each time point to assess the extent of toxicity. Inbred mouse strains selected for their relative sensitivity (male DBA/2Ibg) and resistance (male C57BL/6Ibg) to cocaine-mediated hepatotoxicity were used in this study. Animals were given an acute 50 mg/kg intraperitoneal dose of cocaine, and at various times after administration the hepatic and serum determinations were made. The results of this study confirm the strain difference in cocaine-induced hepatotoxicity and also indicate that there are changes in the biochemistry of the liver that are brought about by acute cocaine administration. In particular, depletions of hepatic GSH, NADH, NADPH and ATP coupled with significant increases in oxidized glutathione were observed in the DBA mouse. C57BL mice showed similar decreases in reduced glutathione, NADH and NADPH but exhibited no significant depletion of hepatic ATP. A similar extent of lipid peroxidation was seen in both mouse strains after cocaine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

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The perturbation of hepatic glutathione by α2-adrenergic agonists

Cited by 19 publications

References 20 publications

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Plasma Cocaine Metabolite and Liver CYP450 3A4 Isoenzyme Levels as Indicators of Cocaine Dependence in Rats Treated with Nutritional Supplements

Metabolism-dependent hepatotoxicity of methimazole in mice depleted of glutathione

Hepatic biochemical changes as a result of acute cocaine administration in the mouse

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