Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum

Açıkgöz, Osman; Gönenç, Sevil; Kayatekin, Berkant Muammer; Uysal, Nazan; Pekçetin, Çetin; Şemin, İlgi; Güre, Ataman

doi:10.1016/s0006-8993(98)01020-8

Cited by 59 publications

(37 citation statements)

References 13 publications

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“…Dopamine levels (previously reported by Wilson et al, 1996 andMoszczynska et al, 2004) Kim et al, 1999;Kita et al, 2000;Wan et al, 2000;Gluck et al, 2001;Flora et al, 2002;Iwashita et al, 2004). Nevertheless, the possibility also has to be considered that chronic drug exposure (e.g., involving tolerance, sensitization) might also have modulated the effects of an acute exposure, as suggested by some animal data (Acikgoz et al, 1998(Acikgoz et al, , 2000. Our working model, based on animal findings, was that the aldehyde increase would be inversely related to the extent of tissue dopamine depletion, which we suspect is an index of the severity of a pharmacological action of MA, and would be more marked in dopamine-rich versus -poor regions.…”

Section: Discussionmentioning

confidence: 91%

“…Although only a nonsignificant trend for a positive association between brain levels of total MA and concentrations of the aldehydes could be observed, the subgroup of MA users having high brain drug levels had significantly higher concentrations of the aldehydes. To the extent that brain levels of MA are representative of amount of recent drug use, this suggests that part of the aldehyde increase could be explained by an acute (e.g., hours to days) exposure to MA as is the case in animal models (Acikgoz et al, 1998(Acikgoz et al, , 2000Jayanthi et al, 1998;Yamamoto and Zhu, TABLE 3 Levels of HNE and MDA in brain of human chronic methamphetamine users subgrouped according to the brain drug level (methamphetamine plus metabolite amphetamine) Data are in mean Ϯ S.E.M. Brain (occipital cortex) drug levels for the high and low groups are 124 Ϯ 47 (range, 20 -319; median 90) and 10.0 Ϯ 1.3 (range, 2.8 -15.6; median 10) nmol/g tissue, respectively (p Ͻ 0.01, Mann-Whitney U tests).…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesized that, as in most of the experimental animal studies in which MDA or MDA-like thiobarbituric acid reactive substances (TBARS) were reported to be increased in brain of MA-treated rodents (Acikgoz et al, 1998(Acikgoz et al, , 2000Jayanthi et al, 1998;Yamamoto and Zhu, 1998;Kim et al, 1999;Kita et al, 2000;Wan et al, 2000;Gluck et al, 2001;Flora et al, 2002;Iwashita et al, 2004), levels of both oxidative markers would be above-normal in the dopamine-rich caudate nucleus of human MA users but less markedly increased (if at all) in brain areas having very low (frontal and cerebellar cortices) concentrations of dopamine. Our human post mortem data provide additional support to the notion based on animal models that MA can cause oxidative damage in human brain.…”

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confidence: 99%

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Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Fitzmaurice

Tong²,

Yazdanpanah³

et al. 2006

J Pharmacol Exp Ther

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Animal studies suggest that the widely used psychostimulant drug methamphetamine (MA) can harm brain dopamine neurones, possibly by causing oxidative damage. However, evidence of oxidative damage in brain of human MA users is lacking. We tested the hypothesis that levels of two "gold standard" products generated from lipid peroxidation, 4-hydroxynonenal (one of the most reactive lipid peroxidation aldehyde products) and malondialdehyde, would be elevated in post mortem brain of 16 dopamine-deficient chronic MA users compared with those in 21 matched control subjects. Derivatized aldehyde concentrations were determined by gas chromatography-mass spectrometry. In the MA group, we found significantly increased levels of 4-hydroxynonenal and malondialdehyde in the dopamine-rich caudate nucleus (by 67 and 75%, respectively) and to a lesser extent in frontal cortex (48 and 36%, respectively) but not in the cerebellar cortex. Approximately half of the MA users had levels of 4-hydroxynonenal falling above the upper limit of the control range in caudate and frontal cortex. A subgroup of MA users with high brain drug levels had higher concentrations of the aldehydes. Our data suggest that MA exposure in human causes, as in experimental animals, above-normal formation of potentially toxic lipid peroxidation products in brain. This provides evidence for involvement of oxygen-based free radicals in the action of MA in both dopamine-rich (caudate) and -poor (cerebral cortex) areas of human brain.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Fitzmaurice

Tong²,

Yazdanpanah³

et al. 2006

J Pharmacol Exp Ther

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“…14). This possibility is also relevant to the neurotoxic amphetamines because their damaging effects on neurons can involve the superoxide radical (15)(16)(17). ONOO Ϫ may be more toxic to cells and proteins than either of its precursors NO and superoxide radical, and ONOO Ϫ has been implicated in neuronal toxicity (18 -19) and neurodegenerative diseases (20 -23).…”

mentioning

confidence: 99%

Peroxynitrite Inactivates Tryptophan Hydroxylase via Sulfhydryl Oxidation

Kuhn

Geddes

1999

Journal of Biological Chemistry

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Tryptophan hydroxylase, the initial and rate-limiting enzyme in serotonin biosynthesis, is inactivated by peroxynitrite in a concentration-dependent manner. This effect is prevented by molecules that react directly with peroxynitrite such as dithiothreitol, cysteine, glutathione, methionine, tryptophan, and uric acid but not by scavengers of superoxide (superoxide dismutase), hydroxyl radical (Me 2 SO, mannitol), and hydrogen peroxide (catalase). Assuming simple competition kinetics between peroxynitrite scavengers and the enzyme, a second-order rate constant of 3.4 ؋ 10 4 M ؊1 s ؊1 at 25°C and pH 7.4 was estimated. The peroxynitrite-induced loss of enzyme activity was accompanied by a concentration-dependent oxidation of protein sulfhydryl groups. Peroxynitrite-modified tryptophan hydroxylase was resistant to reduction by arsenite, borohydride, and dithiothreitol, suggesting that sulfhydryls were oxidized beyond sulfenic acid. Peroxynitrite also caused the nitration of tyrosyl residues in tryptophan hydroxylase, with a maximal modification of 3.8 tyrosines/monomer. Sodium bicarbonate protected tryptophan hydroxylase from peroxynitrite-induced inactivation and lessened the extent of sulfhydryl oxidation while causing a 2-fold increase in tyrosine nitration. Tetranitromethane, which oxidizes sulfhydryls at pH 6 or 8, but which nitrates tyrosyl residues at pH 8 only, inhibited tryptophan hydroxylase equally at either pH. Acetylation of tyrosyl residues with N-acetylimidazole did not alter tryptophan hydroxylase activity. These data suggest that peroxynitrite inactivates tryptophan hydroxylase via sulfhydryl oxidation. Modification of tyrosyl residues by peroxynitrite plays a relatively minor role in the inhibition of tryptophan hydroxylase catalytic activity.Tryptophan hydroxylase (TPH, 1 EC 1.14.16.4; L-tryptophan,tetrahydrobiopterin:oxygen oxidoreductase (5-hydroxylating)) is the initial and rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin. The physiological roles for serotonin are diverse and include modulation of sleep, thermoregulation, and food intake (1). From a clinical perspective, alterations in serotonin function have been implicated in several neuropsychiatric disorders such as depression, obsessive-compulsive disorder, and suicide (2). Alterations in TPH activity produce corresponding changes in the synaptic levels of serotonin (3), suggesting that TPH can have influences on serotonin neurochemical function that extend well beyond its role in fulfilling the first step in serotonin synthesis from tryptophan. Drugs that cause long term changes in TPH activity could well change serotonin synaptic function to the detriment of normal physiological and behavioral function. For example, the neurotoxic amphetamines methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") significantly reduce TPH activity and serotonin levels (4). Long term abuse of these drugs produces behavioral and psychiatric conditions indicative of diminished serotonin function (5, 6). Because the...

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“…This MA induced neurotoxicity may in part be related to the generation of reactive oxygen or nitrogen species (Davidson et al 2001). For example, the acute administration of MA to rodents resulted in production of oxidative stress as demonstrated by reduced glutathione and increased oxidized glutathione levels in the rat striatum and prefrontal cortex (Acikgoz et al 1998, Harold et al 2000. MA induced oxidative stress in mice has also been observed to activate redox-responsive transcription factors such as activator protein-1 (AP-1) and cAMPresponsive element binding protein (CREB) (Lee et al 1999).…”

Section: Methamphetamine Neurotoxicitymentioning

confidence: 99%

Methamphetamine: A molecular and pathological exacerbate of HIV neurocognitive disorder

et al. 2005

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-The use of the recreational drug methamphetamine is becoming more widespread, and it is accompanied by unsafe sexual behaviours that increase the transmission of the human immunodeficiency virus (HIV). This article reviews the available literature of the effect of methamphetamine on the HIV infected brain, and in particular the molecular disturbances and neuropathology associated within this cohort. Our molecular research indicates that methamphetamine and HIV have a synergistic pathological impact on neuronal cell injury and death, which may be mediated by an upregulation of interferon inducible genes observed within this group, thereby contributing to the neurocognitive deficits observed in clinical populations of HIV infected methamphetamine abusers.

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Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum

Cited by 59 publications

References 13 publications

Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Levels of 4-Hydroxynonenal and Malondialdehyde Are Increased in Brain of Human Chronic Users of Methamphetamine

Peroxynitrite Inactivates Tryptophan Hydroxylase via Sulfhydryl Oxidation

Methamphetamine: A molecular and pathological exacerbate of HIV neurocognitive disorder

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