The influence of heroin abuse on glutathione-dependent enzymes in human brain

Gutowicz, Marzena; Kaźmierczak, Beata; Barańczyk‐Kuźma, Anna

doi:10.1016/j.drugalcdep.2010.06.020

Cited by 28 publications

(13 citation statements)

References 30 publications

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“…From these effects, it can be argued that opioid induced hepato- and nephro-toxicity was associated with oxidative stress and Bacopa monnieri due to its strong antioxidant potential reduced this oxidative stress resulting in the amelioration of morphine and street heroin induced hepatotoxicity and nephrotoxicity. Furthermore, heroin abuse increases the activities of glutathione-S-transferase, selenium independent glutathione peroxidase and decreases the level of glutathione therefore mediates oxidative stress in parietal, occipital, frontal and temporal cortex, hippocampus, brain stem and white matter of the brain ( Gutowicz et al, 2011 ). Bacopa monnieri by virtue of antioxidant effect of its major component, bacoside-A inhibits morphine induced brain oxidative stress by improving the activity of ATPases and maintaining the sodium, potassium, calcium and magnesium ionic equilibrium ( Sumathi et al, 2011 ) as well as normalizing the activities of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase ( Sumathy et al, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity

Shahid

Subhan

Ullah

et al. 2016

Heliyon

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The present study examined the hepatotoxicity and nephrotoxicity of morphine and illicit street heroin and their amelioration by a standardized methanolic extract of Bacopa monnieri (L.) (mBME) in rats. Morphine or street heroin was administered at a dose of 20 mg/kg for 14 and 21 days. mBME (40 mg/kg) or ascorbic acid (50 mg/kg) was administered two hours before morphine or street heroin. High performance liquid chromatography (HPLC) was used for the standardization of bacoside-A major components in mBME. The antioxidant potential of mBME was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Administration of morphine and street heroin resulted in marked elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine. Histopathological changes induced by morphine and street heroin after 14 days were of reversible nature while treatment for 21 days was associated with irreversible changes. Pretreatment with mBME or ascorbic acid restored the elevation of serum ALT, AST and creatinine and protected liver and kidneys from the toxicological influence of morphine and street heroin. HPLC analysis showed that mBME contained bacoside-A major components i.e. bacoside-A3 (37.5 μg/mg), bacopaside-II (4.62 μg/mg) and bacopasaponin-C (1.91 μg/mg). The EC50 for the DPPH free radical scavenging assay revealed that mBME possessed strong antioxidant potential. These results concluded that as compared to morphine, street heroin was associated with severe biochemical and histopathological changes in the liver and kidneys. Bacopa monnieri having strong antioxidant potential may provide a beneficial herbal remedy for the efficient management of opioid related hepatotoxicity and nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity

Shahid

Subhan

Ullah

et al. 2016

Heliyon

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“…In light of the influence of redox on methylation of DNA (and histones), the ability of morphine to modulate GSH/GSSG and SAM/SAH provides an example of how epigenetic status can be altered by drugs of abuse. Alcohol induces similar effects by lowering GSH levels and impairing methylation (Waly et al, 2011), whereas cocaine , amphetamine (Carvalho et al, 2001), and heroin (Gutowicz et al, 2011) also alter GSH levels. Although our results implicate MOR-mediated regulation of EAAT3 as the proximal event for morphine-induced changes in DNA methylation, other drugs of abuse may produce redox changes via uniquely different mechanisms.…”

Section: Morphine-induced Epigenetic Changes Via Eaat3mentioning

confidence: 99%

Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake

et al. 2014

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Canonically, opioids influence cells by binding to a G proteincoupled opioid receptor, initiating intracellular signaling cascades, such as protein kinase, phosphatidylinositol 3-kinase, and extracellular receptor kinase pathways. This results in several downstream effects, including decreased levels of the reduced form of glutathione (GSH) and elevated oxidative stress, as well as epigenetic changes, especially in retrotransposons and heterochromatin, although the mechanism and consequences of these actions are unclear. We characterized the acute and long-term influence of morphine on redox and methylation status (including DNA methylation levels) in cultured neuronal SH-SY5Y cells. Acting via m-opioid receptors, morphine inhibits excitatory amino acid transporter type 3-mediated cysteine uptake via multiple signaling pathways, involving different G proteins and protein kinases in a temporal manner. Decreased cysteine uptake was associated with decreases in both the redox and methylation status of neuronal cells, as defined by the ratios of GSH to oxidized forms of glutathione and S-adenosylmethionine to S-adenosylhomocysteine levels, respectively. Further, morphine induced global DNA methylation changes, including CpG sites in long interspersed nuclear elements (LINE-1) retrotransposons, resulting in increased LINE-1 mRNA. Together, these findings illuminate the mechanism by which morphine, and potentially other opioids, can influence neuronal-cell redox and methylation status including DNA methylation. Since epigenetic changes are implicated in drug addiction and tolerance phenomenon, this study could potentially extrapolate to elucidate a novel mechanism of action for other drugs of abuse.

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“…Heroin has been reported to cause hypoxia (6,10), and this is claimed as a reason for creating the oxidative stress condition (7). Increased oxidative stress seems to be a reason for the shift of the balance to oxidizing conditions.…”

Section: Discussionmentioning

confidence: 99%

Thiol/disulphide homeostasis in men with heroin addiction

Kotan¹,

Yılmaz²,

Neşeli̇oğlu³

et al. 2017

Dusunen Adam

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Thiol/disulphide homeostasis in men with heroin addictionObjective: Heroin addicts have increased oxidative stress which can disturb thiol/disulfide (SH/SS) homeostasis, causing disulfide formation. No study has determined the serum thiol amount and blood disulfide amount in heroin addicts. The aim of the study was to investigate dynamic SH/SS homeostasis in heroin addicts.Methods: Serum SH/SS statuses of 31 heroin addicts and 31 healthy controls were compared to determine the changes in SH/SS homeostasis in heroin addicts. Blood serum native thiol and total thiol (ToSH) levels were measured and the disulfide bond amount was calculated as the half value of the difference between native thiol and ToSH levels. For comparison t-test was used.Results: SH and ToSH levels were significantly lower (p<0.001 for both) in heroin addicts than in the healthy group whereas disulfide levels were significantly higher (p<0.001). Heroin addicts had significantly higher SS/ToSH and SS/SH ratios and significantly lower SH/ToSH ratios than healthy individuals. Conclusion:The results showed that SH and ToSH levels were decreased in heroin addicts and SH/SS homeostasis was also disturbed with a shift to the disulfide bond formation side. Results of this study could contribute to the knowledge about pathogenesis of heroin addiction and also to its management. We suggest that replacement of the thiol gap and reduction of excess SS might have positive effects in treatment results.Keywords: Addiction, disulfide, heroin, oxidative stress, thiol ÖZET Eroin bağımlısı erkeklerde tiol/disülfit homeostaziAmaç: Eroin bağımlılığının oksidatif stres artışı ile ilişkili olduğu bilinmektedir. Oksidatif stres disülfit oluşumuna yol açarak tiol/disülfit (SH/SS) homeostazını bozabilir ve böylece protein işlevlerinde değişimlere neden olabilir. Eroin bağımlılarında serum tiol miktarı ve kan disülfit miktarının araştırıldığı bir çalışma mevcut değildir. Bu çalışmanın amacı eroin bağımlılığında dinamik SH/SS homeostazını incelemektir.Yöntem: Otuz bir eroin bağımlısı erkek ve otuz bir sağlıklı erkekte natif tiol-disülfit değişimlerini içeren kan SH/SS homeostazı incelendi. Serum natif tiol ve total tiol (ToSH) düzeyleri ölçüldü; natif tiol ve ToSH düzeyleri farkının yarı değeri olarak disülfit bağ düzeyi hesaplandı. Karşılaştırmalar t testi ile yapıldı.Bulgular: Eroin bağımlısı erkeklerde SH ve ToSH konsantrasyonları kontrollere göre daha düşük (her ikisi için p<0.001) ve SS düzeyleri daha yüksek (p=0.001) saptandı. Eroin bağımlılarında SS/ToSH ve SS/SH oranları sağlıklı erkeklerden daha yüksek (her ikisi için p<0.001) ve SH/ToSH oranı daha düşük (p<0.001) saptandı.Sonuç: Çalışmanın sonuçları serum SH ve ToSH düzeylerinin eroin bağımlısı erkeklerde azalmış olduğu ve SH/SS homeostazının disülfit bağı oluşumu yönünde bozulduğunu göstermektedir. Bu sonuçlar eroin bağımlılığı patogenezi ve eroin bağımlılığına yaklaşım açısından katkı sağlayabilir. Eroin bağımlılığının tedavi sürecinde tiol eksikliğinin yerine konması ve aşırı disülfit miktarının azal...

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The influence of heroin abuse on glutathione-dependent enzymes in human brain

Cited by 28 publications

References 30 publications

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity

Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake

Thiol/disulphide homeostasis in men with heroin addiction

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