Abstract：
: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.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Farina M,Soares FA,Zeni G,Souza DO,Rocha JBdoi
10.1016/j.toxlet.2003.10.001keywords:
subject
Has Abstractpub_date
2004-02-02 00:00:00pages
227-35issue
3eissn
0378-4274issn
1879-3169pii
S0378427403003709journal_volume
146pub_type
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journal_title：Toxicology letters
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doi：10.1016/0378-4274(85)90096-7
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
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journal_title：Toxicology letters
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pub_type： 杂志文章,评审
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更新日期：1995-12-01 00:00:00
