Article

Lipid peroxidation in presence of ebselen.

Lehrstuhl für Organische Chemie I, Universität Bayreuth, Bayreuth, Germany.
Chemistry and Physics of Lipids (impact factor: 2.57). 08/1997; 87(2):149-58. DOI:10.1016/S0009-3084(97)00037-6
Source: PubMed

ABSTRACT Lipid peroxidation is initiated by cell damage. After homogenisation of porcine heart tissue in aqueous solution we observed the same lipid peroxidation products as detected after heart infarction. We used this observation to study the influence of ebselen (2-phenyl-1,2-benzoisoselenazol-3-(2H)-one) on the generation of oxidatively derived monohydroxy fatty acids and alpha-hydroxyaldehydes, typical lipid peroxidation (LPO) products. Heart tissue was homogenised before and after enzyme destruction and with addition of ebselen. The obtained LPO products were analysed by GC/MS after appropriate derivatisation and quantified by using internal standards. The amount of monohydroxy fatty acids and alpha-hydroxyaldehydes increased considerably in the porcine heart homogenates in which the enzymes were kept active. Addition of ebselen caused an additional significant increase of hydroxy fatty acids, while the increase of aldehydic compounds was less. These results confirm the glutathione peroxidase-like activity of ebselen but demonstrate also that it does not prevent lipid peroxidation.

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    Article: Multifunctional Ebselen drug functions through the activation of DNA damage response and alterations in nuclear proteins.
    Gajendra K Azad, Shah Jaimin Balkrishna, Narayanan Sathish, Sangit Kumar, Raghuvir S Tomar
    [show abstract] [hide abstract]
    ABSTRACT: Several studies have demonstrated that Ebselen is an anti-inflammatory and anti-oxidative agent. Contrary to this, studies have also shown a high degree of cellular toxicity associated with Ebselen usage, the underlying mechanism of which remains less understood. In this study we have attempted to identify a possible molecular mechanism behind the above by investigating the effects of Ebselen on Saccharomyces cerevisiae. Significant growth arrest was documented in yeast cells exposed to Ebselen similar to that seen in presence of DNA damaging agents (including methyl methane sulfonate [MMS] and hydroxy urea [HU]). Furthermore, mutations in specific lysine residues in the histone H3 tail (H3 K56R) resulted in increased sensitivity of yeast cells to Ebselen presumably due to alterations in post-translational modifications of histone proteins towards regulating replication and DNA damage repair. Our findings suggest that Ebselen functions through activation of DNA damage response, alterations in histone modifications, activation of checkpoint kinase pathway and derepression of ribonucleotide reductases (DNA repair genes) which to the best of our knowledge is being reported for the first time. Interestingly subsequent to Ebselen exposure there were changes in global yeast protein expression and specific histone modifications, identification of which is expected to reveal a fundamental cellular mechanism underlying the action of Ebselen. Taken together these observations will help to redesign Ebselen-based therapy in clinical trials.
    Biochemical pharmacology 01/2012; 83(2):296-303. · 4.25 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

additional significant increase
 
aldehydic compounds
 
aqueous solution
 
cell damage
 
ebselen
 
enzyme destruction
 
enzymes
 
glutathione peroxidase-like activity
 
homogenisation
 
hydroxy fatty acids
 
internal standards
 
lipid peroxidation
 
lipid peroxidation products
 
monohydroxy fatty acids
 
obtained LPO products
 
oxidatively
 
porcine heart homogenates
 
porcine heart tissue
 
typical lipid peroxidation
 

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