دورية أكاديمية
أعرض في EDS

Inhibition of LDL oxidation and oxidized LDL-induced cytotoxicity by dihydropyridine calcium antagonists.

التفاصيل البيبلوغرافية
العنوان: Inhibition of LDL oxidation and oxidized LDL-induced cytotoxicity by dihydropyridine calcium antagonists.
المؤلفون: Sevanian A; University of Southern California, School of Pharmacy, Dept. Molecular Pharmacology & Toxicology, Los Angeles 90033, USA. asevan@hsc.usc.edu, Shen L, Ursini F
المصدر: Pharmaceutical research [Pharm Res] 2000 Aug; Vol. 17 (8), pp. 999-1006.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, P.H.S.
اللغة: English
بيانات الدورية: Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 8406521 Publication Model: Print Cited Medium: Print ISSN: 0724-8741 (Print) Linking ISSN: 07248741 NLM ISO Abbreviation: Pharm Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers
Original Publication: Stuttgart ; New York : Thieme, c1984-
مواضيع طبية MeSH: Calcium Channel Blockers/*pharmacology , Dihydropyridines/*pharmacology , Lipid Peroxidation/*drug effects , Lipoproteins, LDL/*antagonists & inhibitors , Lipoproteins, LDL/*metabolism, Animals ; Antioxidants/chemistry ; Ascorbic Acid/chemistry ; Calcium/metabolism ; Cell Survival/drug effects ; Cells, Cultured ; Endothelium, Vascular/cytology ; Fluorescent Dyes ; Kinetics ; Lipoproteins, LDL/toxicity ; Oxidation-Reduction ; Rabbits ; Reactive Oxygen Species/physiology ; Vitamin E/chemistry
مستخلص: Purpose: The antioxidant activity of dihydropyridine calcium channel antagonists was evaluated based on LDL oxidation kinetics, oxidative cell injury associated with reactive species generation, and increases in free intracellular calcium (Ca2+) levels. Interactions with ascorbic acid were studied under conditions representative of LDL oxidation in plasma and tissue.
Methods: Analysis of antioxidant activity utilized measurements of one-electron oxidation potentials and scavenging of peroxy radical-mediated oxidation. LDL antioxidant potency was determined spectrophotometrically using copper-mediated oxidation kinetics in the absence and presence of 100 microM ascorbic acid. Prevention of oxidant-induced endothelial cell injury was determined from the formation of reactive oxygen species generation and increases in intracellular free calcium concentrations following addition of oxidized LDL or linoleic acid hydroperoxide.
Results: Felodipine and amlodipine effectively inhibit peroxyl radical-mediated oxidation in lipoproteins and cells that is markedly enhanced in the presence of ascorbic acid. In the presence of ascorbic acid, inhibition of LDL oxidation is over four times greater than in LDL treated without antioxidants, and oxidized LDL and linoleic acid hydroperoxide-induced reactive oxygen species formation is effectively suppressed in cells. Inhibition of intracellular calcium increases was achieved using nM concentrations of felodipine or amlodipine.
Conclusions: The additive effect for ascorbic acid and the calcium channel antagonist is postulated to involve a combination of peroxide-degrading and peroxyl radical scavenging reactions, demonstrating the importance of lipid peroxides during LDL oxidation and oxidized LDL-induced cytotoxicity. Cytoprotection is associated with inhibition of oxidant-induced increases in intracellular free calcium. Both the cytoprotective and LDL antioxidant activity for these compounds is manifested at concentrations approaching the therapeutic levels found in plasma.
References: Eur J Clin Pharmacol. 1998 Oct;54(8):603-7. (PMID: 9860146)
Free Radic Biol Med. 1998 Mar 1;24(4):607-23. (PMID: 9559873)
Toxicol Appl Pharmacol. 1993 May;120(1):29-36. (PMID: 8511780)
J Lipid Res. 1994 Apr;35(4):669-77. (PMID: 8006522)
Cardiovasc Drugs Ther. 1996 Sep;10(4):417-24. (PMID: 8924055)
Cytobios. 1999;99(391):83-95. (PMID: 10582325)
FEBS Lett. 1999 Apr 1;448(1):49-52. (PMID: 10217408)
Arch Biochem Biophys. 1995 Oct 20;323(1):97-107. (PMID: 7487079)
Clin Biochem. 1979 Feb;12(1):22-6. (PMID: 36239)
Free Radic Biol Med. 1992;12(3):183-7. (PMID: 1314212)
Free Radic Biol Med. 1997;23(4):680-94. (PMID: 9215814)
Free Radic Biol Med. 1994 Oct;17(4):285-95. (PMID: 8001833)
Arch Biochem Biophys. 1989 Nov 1;274(2):443-52. (PMID: 2552924)
J Hypertens. 1998 Dec;16(12 Pt 2):1913-9. (PMID: 9886877)
Hypertens Res. 1996 Dec;19(4):223-8. (PMID: 8986452)
Biochim Biophys Acta. 1995 Aug 3;1257(3):279-87. (PMID: 7647104)
Arterioscler Thromb Vasc Biol. 1999 Jan;19(1):98-105. (PMID: 9888871)
Anal Biochem. 1992 Mar;201(2):375-80. (PMID: 1632527)
Biochem Pharmacol. 1996 Jan 26;51(2):141-50. (PMID: 8615882)
Hypertens Res. 1995 Mar;18(1):47-53. (PMID: 7584910)
Biochem Pharmacol. 1989 Dec 1;38(23):4344-8. (PMID: 2597206)
J Chromatogr B Biomed Appl. 1994 Mar 18;654(1):129-33. (PMID: 8004234)
Trends Biochem Sci. 1999 Jun;24(6):219-23. (PMID: 10366846)
Arch Biochem Biophys. 1992 Sep;297(2):265-70. (PMID: 1497346)
Biochim Biophys Acta. 1991 Sep 11;1085(2):159-66. (PMID: 1892884)
Free Radic Biol Med. 1998 May;24(7-8):1228-34. (PMID: 9626578)
Am J Clin Nutr. 1995 Dec;62(6 Suppl):1322S-1326S. (PMID: 7495227)
Biochem Pharmacol. 1998 Jun 1;55(11):1843-52. (PMID: 9714303)
Free Radic Res. 1998 Jun;28(6):601-9. (PMID: 9736312)
معلومات مُعتمدة: HL50350 United States HL NHLBI NIH HHS
المشرفين على المادة: 0 (Antioxidants)
0 (Calcium Channel Blockers)
0 (Dihydropyridines)
0 (Fluorescent Dyes)
0 (Lipoproteins, LDL)
0 (Reactive Oxygen Species)
1406-18-4 (Vitamin E)
PQ6CK8PD0R (Ascorbic Acid)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20001012 Date Completed: 20010215 Latest Revision: 20190818
رمز التحديث: 20240627
DOI: 10.1023/a:1007539607613
PMID: 11028948
قاعدة البيانات: MEDLINE
الوصف
تدمد:0724-8741
DOI:10.1023/a:1007539607613