Adjuvant Potential of Selegiline in Attenuating Organ Dysfunction in Septic Rats with Peritonitis

Tsao, Cheng Ming; Jhang, Jhih-Gang; Chen, Shiu-Jen; Ka, Shuk‐Man; Wu, Tsu‐Juey; Liaw, Wen‐Jinn; Huang, Hsieh-Chou; Wu, Chin-Pyng

doi:10.1371/journal.pone.0108455

Cited by 11 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Widely used in the treatment of Parkinson's disease [10], selegiline is an irreversible inhibitor with selectivity for monoamine oxidase type B (MAO-B) that in recent studies showed anti-inflammatory and anti-apoptotic properties [11]. It has been shown to reduce total brain damage after transient hypoxiaischaemia, to maintain mitochondrial membrane potential, and to eliminate oxygen radicals [12].…”

Section: Introductionmentioning

confidence: 99%

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke

Bartolo

Zucchella

Capone

et al. 2015

Journal of the Neurological Sciences

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke

Bartolo

Zucchella

Capone

et al. 2015

Journal of the Neurological Sciences

View full text Add to dashboard Cite

“…Previous studies showed that selegiline prevents ROS production and lipid peroxidation . A research by Tsao and colleagues revealed that selegiline is a potential adjuvant therapy for the treatment of sepsis by attenuating the oxidative and nitrosative stress, decreasing acidosis and inflammation, and rescuing organ failure including heart failure …”

Section: Discussionmentioning

confidence: 99%

“…Also, our histopathological results in cardiac tissue suggest that selegiline at lower doses (1, 5 mg/kg) prevents the infiltration of lymphocyte into interstitium. Moreover, other reports showed that selegiline reduced neutrophil infiltration into the liver and lung in an animal model of caecal ligation and puncture‐induced sepsis . Inhibition of acetylcholinesterase (ACE) in the brain is one of the mechanisms through which AlP exerts its toxic effects .…”

Section: Discussionmentioning

confidence: 99%

“…38 A research by Tsao and colleagues revealed that selegiline is a potential adjuvant therapy for the treatment of sepsis by attenuating the oxidative and nitrosative stress, decreasing acidosis and inflammation, and rescuing organ failure including heart failure. 39 PH 3 inhibits cytochrome c oxidase (complex IV) of electron transport chain (ETC) and reduces mitochondrial membrane potential (ΔΨm). It also reduces the activity of complexes I and II and disrupts the synthesis of ATP leading to energy insufficiency.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats

Maleki

Hosseini

Rahimi

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti‐apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP‐induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.

show abstract

“…As a selective MAO-B inhibitor, selegiline may be used as an anti-PD drug to exert antioxidant and anti-apoptotic effects (29,30). It has also been indicated that selegiline decreases oxidative stress and cell death induced by 1-methyl-4-phenylpyridinium (MPP + ), an inducing agent of PD (31).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

et al. 2017

View full text Add to dashboard Cite

Abstract. Oxidative stress and reactive oxygen species generation have been implicated in the pathogenesis of several neurological disorders including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. In the present study, the neuroprotective effects of selegiline against hydrogen peroxide-induced oxidative stress in hippocampus-derived neural stem cells (NSCs) were evaluated. NSCs isolated from neonatal Wistar rats were pretreated with different doses of selegiline for 48 h and then exposed to 125 µM H 2 O 2 for 30 min. Using MTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, acridine orange/ethidium bromide staining and reverse transcription-quantitative polymerase chain reaction, the effects of selegiline on cell survival, apoptosis and the expression of B-cell lymphoma 2 (Bcl-2) and heat shock protein 4 (Hspa4) in pretreated stem cells were assessed compared with a control group lacking pretreatment. The results indicated that the viability of cells pretreated with 20 µM selegiline was significantly increased compared with the control group (P<0.05). Additionally, 20 µM selegiline increased the mRNA expression of Bcl-2 and Hspa4 (P<0.05 vs. control) and suppressed oxidative stress-induced cell death (apoptosis and necrosis; P<0.05 vs. control and 10 µM groups). From these findings, it was concluded that selegiline may be a therapeutic candidate for the treatment of neurological diseases mediated by oxidative stress. IntroductionThe most common neorodegenerative disorders, namely Alzheimer's disease (AD) and Parkinson's disease (PD), are prevalent in ~1% of individuals aged 60 years and older (1). Their etiologies remain uncertain, though there are a number of established pathogenic factors, including oxidative stress, neural apoptosis, mitochondrial dysfunction, excitotoxicity, impairment of the ubiquitin-proteasome system and inflammation (2,3). Neuroprotective therapy has been suggested to prevent disease progression by inhibiting the action of pathogenic factors, for instance, by reducing the production of reactive oxygen species (ROS) (4). Overproduction of ROS may cause oxidative damage to biomolecules and subsequently DNA damage, ultimately leading to the development of neurodegenerative diseases. According to studies on PD, inhibitors of type B monoamine oxidase (MAO), including selegiline [also known as (-)-deprenyl] and rasagiline, are among the most promising neuroprotective agents identified to date (5-7). MAO exists in two forms, MAO-A and -B. The catalytic activity of these enzymes generates H 2 O 2 and nitrogen species, which are toxic products that may cause oxidative damage to mitochondrial DNA (mtDNA) and thus have potential implications for apoptosis, aging and neurodegenerative processes (8). The MAO-B inhibitor, selegiline, is typically recommended as a first-line treatment for PD and has been demonstrated to possess neuroprotective functions (9); notably, this inhibitor protected neuronal cells against induc...

show abstract

Adjuvant Potential of Selegiline in Attenuating Organ Dysfunction in Septic Rats with Peritonitis

Cited by 11 publications

References 40 publications

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats

Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide

Contact Info

Product

Resources

About