Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain

Goudas, Leonidas C.; Langlade, A.; Serrié, Alain; Matson, Wayne R.; Milbury, Paul E.; Thurel, C; Sandouk, P.; Carr, Daniel B.

doi:10.1213/00000539-199911000-00023

Cited by 76 publications

(19 citation statements)

References 27 publications

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“…This result suggests that the effect was enhanced by the presence of sibutramine and zinc and that both products may protect the brain from endogenously generated oxidative damage [23]. Thus, they may also make the entire central nervous system (CNS) less vulnerable to hydrogen peroxide‐ and hydroxyl radical‐derived oxidative damage, whose production takes place during the normal metabolic pathways in the female CNS [24], as was demonstrated by the reduction in H 2 O 2 in the cortex and hemisphere in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sibutramine on 5‐Hydroxyindole Acetic Acid Levels and Selected Oxidative Biomarkers on Brain Regions of Female Rats in the Presence of Zinc

Guzmán¹,

García²,

Mejía³

et al. 2011

Basic Clin Pharma Tox

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A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 lg ⁄ kg of zinc and 10 mg ⁄ kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H 2 O 2 ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc ⁄ sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H 2 O 2 concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects.Obesity and depression, conditions that were considered a health problem in adults a few years ago, are now recognized as an ordinary disease among young people. In Mexico, the National Nutrition Survey, ENSANUT 2006, reported that the national combined prevalence of overweight and obesity in children from 5 to 11 years of age is about 26% for both sexes, with 26.8% of these being girls and 25.9% boys [1].Recent data from the National Health and Nutrition Examination (USA) have estimated that 17% of the youngsters between 2 and 19 years of age are overweight compared with only 5% found some decades ago [2]. Depression also has an impact on a considerable part of the juvenile population. The prevalence of major depressive disorder has been estimated at 2% in children and 4-8% in adolescents [3].Several studies have pointed out the role played by serotonin not only in obesity but also in depression. Particularly, it has been observed that serotonin plays an important role in the regulation of the processes of satiety and later the ingestion of food and that seasonal changes in the genetic expression of serotonin transporters are related to seasonal appearance of depression in adults [4].On the other hand, it is well known that obesity and depression are accompanied by imbalance between pro-and antioxidant systems of the organism and that this imbalance is related to free radical (FR) generation, which has been associated with the appearance of neurodegenerative diseases to a great extent. In this sense, it has been demonstrated that the serotonergic system also plays an important role in the regulation...

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Section: Discussionmentioning

confidence: 99%

Effect of Sibutramine on 5‐Hydroxyindole Acetic Acid Levels and Selected Oxidative Biomarkers on Brain Regions of Female Rats in the Presence of Zinc

Guzmán¹,

García²,

Mejía³

et al. 2011

Basic Clin Pharma Tox

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“…Many studies have found that morphine and its analogue derivatives alter oxidative metabolism, and a number have shown that morphine causes peroxide generation in vitro and in vivo. Superoxide species have been produced by morphine in polymorphonuclear leucocytes [1], glomerular mesanglial cells [2] and hepatocytes in vitro [3], and antioxidant status has been modified in rat caudate nucleus [4] and cerebral spinal fluid [5] by means of morphine injections.…”

Section: Introductionmentioning

confidence: 99%

Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of α‐lipoic acid administration

Pinelli

Cighetti

Trivulzio

2008

Fundamemntal Clinical Pharma

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A number of experimental studies have found that reactive oxygen species are involved during morphine treatment or withdrawal. The aims of this study were to analyse whether morphine administration and/or removal are related to peroxide generation and/or signs of withdrawal in rats, and whether the changes in antioxidant status induced by the administration of an antioxidant may modify peroxide levels and behavioural signs. We injected morphine or morphine and naloxone into rats and evaluated the plasma levels of peroxide malondialdehyde (MDA) and the appearance of withdrawal signs. We also investigated the effects on these parameters induced by the administration of the antioxidant alpha-lipoic acid (LA). Morphine treatment increased MDA levels. Abrupt naloxone-induced morphine withdrawal caused a further and significant increase in MDA, and the appearance of withdrawal signs such as abnormal fecal excretion, shortened latency times and jumping. The administration of LA lowered MDA levels in the rats treated with morphine or morphine plus naloxone, and also decreased MDA values and abstinence signs in the animals treated with morphine plus naloxone. The effects of LA were attributed to its capacity to scavenge peroxides and interfere with the biogenesis of the arachidonic acid metabolites involved in the expression of abstinence symptoms.

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“…Moreover, it was found that treatment with a potent antioxidant decreased the blood-brain barrier disruption and provided neuroprotection (33). In another study (34) it was found that morphine induces acute central glutathione (GSH) depletion and, therefore, renders the central nervous system vulnerable to damage from free radicals, and it was suggested that this could be the underlying mechanism for the neuropsychiatric toxicity of morphine.…”

Section: Discussionmentioning

confidence: 99%

Isoprostane as a Marker of Oxidative Stress in Chronic Heroin Users: Correlation with Duration of Heroin Use or Concomitant Hepatitis C Infection

Kovatsi

Njau

Nikolaou³

et al. 2010

The American Journal of Drug and Alcohol Abuse

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Acute Decreases in Cerebrospinal Fluid Glutathione Levels after Intracerebroventricular Morphine for Cancer Pain

Cited by 76 publications

References 27 publications

Effect of Sibutramine on 5‐Hydroxyindole Acetic Acid Levels and Selected Oxidative Biomarkers on Brain Regions of Female Rats in the Presence of Zinc

Effect of Sibutramine on 5‐Hydroxyindole Acetic Acid Levels and Selected Oxidative Biomarkers on Brain Regions of Female Rats in the Presence of Zinc

Plasma malondialdehyde levels and opiate withdrawal signs observed in rats treated with morphine plus naloxone: effects of α‐lipoic acid administration

Isoprostane as a Marker of Oxidative Stress in Chronic Heroin Users: Correlation with Duration of Heroin Use or Concomitant Hepatitis C Infection

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