| Ebselen. Antioxidant capacity in renal preservation. | |
| | |
MedLine Citation:
|
PMID: 1610399 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Ebselen (PZ51) was tested for its ability to inhibit oxidative membrane damage and improve outcome of rabbit kidneys rendered cold ischaemic for 72 hr. In view of the rapid metabolism of ebselen, the antioxidant capacities of its two principal metabolites were first compared with that of the parent drug in an in vitro hepatic microsomal lipid peroxidation system initiated by NADPH/Fe(3+)-ADP. The potent antioxidant activity of ebselen was confirmed but metabolite I (2-glucuronylselenobenzanilide) exhibited no antioxidant potential up to a concentration of 50 microM; metabolite II (4-hydroxy-2-methyl-selenobenzanilide) did inhibit lipid peroxidation but was about 80 times less effective than the parent compound. The storage of rabbit kidneys in hypertonic citrate solution at 0 degrees for 72 hr of cold ischaemia resulted in greatly increased susceptibility to oxidative membrane damage in both the cortex and medulla as determined by the subsequent in vitro formation of two markers of lipid peroxidation (Schiff's bases and thiobarbituric acid-reactive material). Inclusion of ebselen (50 microM) in the flush and storage solution led to a highly significant reduction in these oxidative markers in both regions of the kidney. Intracellular and interstitial oedema was noted in organs subjected to 72 hr cold ischaemia and was reduced by ebselen (50 microM in the flush/storage solution). The rate of post-ischaemic lipid peroxidation was found to correlate well with the extent of oedema in the renal medulla (r = 0.84, P less than 0.001) but no such correlation was found in the cortex. Administration of ebselen (5.5 mg/kg i.v. and 100 microM in the flush/storage solution) did not improve the long-term survival of rabbits following autotransplantation of a single kidney stored for 48 or 72 hr. No protective effect of ebselen could be demonstrated either in terms of graded physiological function or histological outcome. |
| | |
Authors:
|
J D Gower; N J Lane; J G Goddard; S Manek; I J Ambrose; C J Green |
Related Documents
:
|
403019 - Formation of lipid peroxides in isolated rat liver microsomes by singlet molecular oxygen. 17145559 - 7-dehydrocholesterol enhances ultraviolet a-induced oxidative stress in keratinocytes: ... 23270549 - Oxidative damage to macromolecules in the thyroid - experimental evidence. 16382569 - Recent advances in the biochemistry and clinical relevance of the isoprostane pathway. 2735939 - Allyl alcohol-induced hemolysis and its relation to iron release and lipid peroxidation. 20836659 - Chemistry and biochemistry of lipid peroxidation products. 2766179 - Excipients in topical corticosteroid preparations in canada. 16659269 - Phosphatidylserine synthesis in castor bean endosperm. 22493939 - Oxidation of low-density lipoprotein by iron at lysosomal ph: implications for atherosc... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Biochemical pharmacology Volume: 43 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 1992 Jun |
Date Detail:
|
Created Date: 1992-07-21 Completed Date: 1992-07-21 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 2341-8 Citation Subset: IM |
Affiliation:
|
Section of Surgical Research, MRC Clinical Research Centre, Harrow, Middlesex, U.K. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antioxidants* Azoles* / administration & dosage, chemistry, pharmacology Cryopreservation* Graft Survival / drug effects Kidney* / metabolism, pathology Kidney Transplantation Lipid Peroxidation / drug effects Male Microsomes / metabolism Organ Preservation / methods* Organoselenium Compounds* / administration & dosage, chemistry, pharmacology Rabbits Rats Rats, Inbred Strains Time Factors |
| Chemical | |
Reg. No./Substance:
|
0/Antioxidants; 0/Azoles; 0/Organoselenium Compounds; 60940-34-3/ebselen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Differential inhibition of hepatic morphine UDP-glucuronosyltransferases by metal ions.
Next Document: Photosensitizing efficiency of two regioisomers of the benzoporphyrin derivative monoacid ring A (BP...