Linked Life Data

14687760

Source:http://linkedlifedata.com/resource/pubmed/id/14687760

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-12-22
pubmed:abstractText
Oxidative stress has been pointed as an important molecular mechanism for liver injury in methylmercury (MeHg) poisoning. Ebselen, a seleno-organic compound that possesses anti-oxidant properties, is a useful therapeutic agent used in clinical situations involving oxidative stress. Here, we examined the possible in vivo protective effect of ebselen against the pro-oxidative effects of MeHg in liver from suckling rat pups. The effects of MeHg exposure (subcutaneous injections of methylmercury chloride: 2 mg/kg) on the hepatic levels of thiobarbituric acid reactive substances (TBARS) and non-ptotein thiols (NPSH), and on liver glutathione peroxidase (GSHPx) activity, as well as the possible antagonist effect of ebselen (10 mg/kg; subcutaneously) against MeHg effects, were evaluated during the post-natal period. In addition, the possible in vitro interaction between ebselen, glutathione (GSH) and MeHg was investigated by light/UV spectroscopy, with particular attention to the formation of complexes involving ebselen selenol intermediate and MeHg. After in vivo exposure, MeHg and ebselen alone increased hepatic TBARS levels. Moreover, simultaneous treatment with both compounds caused a higher increase in hepatic TBARS levels when compared to the treatments with individual compounds. Liver NPSH decreased after treatments with MeHg and ebselen alone. A significant negative correlation between hepatic TBARS and NPSH was observed. MeHg alone decreased liver GSHPx activity and ebselen, which did not affect this variable per se, reverted this inhibitory effect of MeHg. Light/UV spectroscopy showed that ebselen and GSH form a chemical intermediate that regenerates ebselen after MeHg addition. The presented results show that ebselen abolished the MeHg-induced inhibition on liver GSHPx activity, but did not prevent the oxidative effects of MeHg on liver lipids and NPSH. MeHg affects the in vitro interaction between ebselen and GSH and this phenomenon seems to be responsible for its inhibitory effect toward thiol-peroxidase activity. Additionally, ebselen presents pro-oxidative effects on rat liver, pointing to thiol depletion as a molecular mechanism related to ebselen-induced hepatotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
146
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
227-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14687760-Animals, pubmed-meshheading:14687760-Animals, Suckling, pubmed-meshheading:14687760-Antioxidants, pubmed-meshheading:14687760-Azoles, pubmed-meshheading:14687760-Female, pubmed-meshheading:14687760-Glutathione, pubmed-meshheading:14687760-Glutathione Peroxidase, pubmed-meshheading:14687760-Liver, pubmed-meshheading:14687760-Male, pubmed-meshheading:14687760-Mercury Poisoning, pubmed-meshheading:14687760-Methylmercury Compounds, pubmed-meshheading:14687760-Organoselenium Compounds, pubmed-meshheading:14687760-Oxidative Stress, pubmed-meshheading:14687760-Pregnancy, pubmed-meshheading:14687760-Rats, pubmed-meshheading:14687760-Rats, Wistar, pubmed-meshheading:14687760-Spectrophotometry, Ultraviolet, pubmed-meshheading:14687760-Sulfhydryl Compounds, pubmed-meshheading:14687760-Thiobarbituric Acid Reactive Substances
pubmed:year
2004
pubmed:articleTitle
Additive pro-oxidative effects of methylmercury and ebselen in liver from suckling rat pups.
pubmed:affiliation
Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Campus Universitário, Camobi, 97105-900, Santa Maria, RS, Brazil. marcelofarina@zipmail.com.br
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't