DL-trans-3,4-Dihydroxy-1-selenolane (DHS(red)) accelerates healing of indomethacin-induced stomach ulceration in mice.
Summary of "DL-trans-3,4-Dihydroxy-1-selenolane (DHS(red)) accelerates healing of indomethacin-induced stomach ulceration in mice."
Abstract Management of the gastro-toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) remains a crucial problem, because the commercially available anti-ulcer drugs have side effects and are often expensive. Hence, we examined the potential of a new water-soluble GPx mimic, DL-trans-3,4-dihydroxy-1-selenolane (DHS(red)) in healing the indomethacin-induced stomach ulceration in mice. Administration of indomethacin (18 mg/kg, po) induced ulceration in the glandular portion of the gastric mucosa, accompanied by increased lipid peroxidation (1.3 fold, p<0.001) and protein oxidation (1.5 fold, p<0.001), depletion of thiol-defense (42.5%, p<0.01), plasma total antioxidant status (53.4%, p<0.001) and mucin (47.5%, p<0.01), as well as reduced expressions of cyclooxygenases and prostaglandin synthesis (54.7%, p<0.001) in the gastric tissues of mice. Daily oral administration of DHS(red) (2.5 mg/kg) or omeprazole (Omez) (3 mg/kg) for 3 days respectively produced ∼74% and 69% (p<0.001) healing of the acute gastric ulceration. The test samples also significantly reversed all the adverse effects of indomethacin on the biochemical parameters. Apparently, the gastric ulcer healing action of DHS(red) and Omez was due to their antioxidant action, and ability to protect mucin and augment PG synthesis by upregulation of the COX isozymes. The results suggested that the non-toxic and inexpensive compound, DHS(red) may be a good candidate for further evaluation as a potent anti-ulcer drug.
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Journal Details
This article was published in the following journal.
Name: Free radical research
ISSN: 1029-2470
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22867023
- DOI: http://dx.doi.org/10.3109/10715762.2012.718766
Medical and Biotech [MESH] Definitions
Prostaglandins E
(11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.
Zearalenone
(S-(E))-3,4,5,6,8,10-Hexahydro-14,16-dihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione. One of a group of compounds known under the general designation of resorcylic acid lactones. Cis, trans, dextro and levo forms have been isolated from the fungus Gibberella zeae (formerly Fusarium graminearum). They have estrogenic activity, cause toxicity in livestock as feed contaminant, and have been used as anabolic or estrogen substitutes.
Linitis Plastica
A condition where the stomach wall becomes thickened, rubbery and loses its ability to distend. The stomach assumes a "leather bottle" shape. It is most often seen in adenocarcinoma of the stomach. The term is often used synonymously with diffuse adenocarcinoma of the stomach.
Trans-splicing
The joining of RNA from two different genes. One type of trans-splicing is the "spliced leader" type (primarily found in protozoans such as trypanosomes and in lower invertebrates such as nematodes) which results in the addition of a capped, noncoding, spliced leader sequence to the 5' end of mRNAs. Another type of trans-splicing is the "discontinuous group II introns" type (found in plant/algal chloroplasts and plant mitochondria) which results in the joining of two independently transcribed coding sequences. Both are mechanistically similar to conventional nuclear pre-mRNA cis-splicing. Mammalian cells are also capable of trans-splicing.
Trans-cinnamate 4-monooxygenase
A member of the P450 superfamily, this enzyme catalyzes the first oxidative step of the phenylpropanoid pathway in higher PLANTS by transforming trans-cinnamate into p-coumarate.
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