ANTI‐OXIDANT MECHANISMS OF KOLAVIRON: STUDIES ON SERUM LIPOPROTEIN OXIDATION, METAL CHELATION AND OXIDATIVE MEMBRANE DAMAGE IN RATS

Clinical and Experimental Pharmacology and Physiology - Tập 32 Số 8 - Trang 667-674 - 2005
E. Olatunde Farombi1, IA Nwaokeafor1
1Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria

Tóm tắt

SUMMARY

1. In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate‐induced damage to microsomal lipids was investigated.

2. Lipoprotein resistance to copper‐induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron‐treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron‐treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron‐treated rats with an attendant significant increase in the total anti‐oxidant activity compared with control.

3. In vitro, kolaviron (10–60 µmol/L) inhibited the Cu2+‐induced oxidation of rat serum lipoprotein in a concentration‐dependent manner. Kolaviron, at 20 and 60 µmol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 µmol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 µmol/L) elicited a 53% increase in lag time, whereas 40 and 60 µmol/L kolaviron produced 38 and 88% decreases in slope, respectively.

4. Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration‐dependent manner. Kolaviron at the highest dose tested (90 µmol/L) had a significant chelating effect on Fe2+ (78%).

5. In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti‐oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis.

Từ khóa


Tài liệu tham khảo

10.1016/S0955-2863(02)00252-8

10.1021/jf0010533

10.1016/0891-5849(95)02173-6

10.1016/0891-5849(92)90181-F

10.1016/S0891-5849(99)00018-0

10.1016/0006-2952(96)00107-4

Knet P, 1994, Antioxidant vitamin intake and coronary mortality in a longitudinal population study, Am. J. Epidemiol., 139, 1180, 10.1093/oxfordjournals.aje.a116964

10.1016/S0021-9150(00)00625-0

Harbone JB, 1986, Plant Flavonoids in Biology and Medicine., 15

10.1016/0891-5849(95)02227-9

10.1016/0140-6736(93)92876-U

Hutchinson J, 1956, Flora of West Tropical Africa

Iwu M, 1982, Traditional Igbo Medicine.

Ayensu ES, 1978, Medicinal Plants of West Africa.

10.1016/0378-8741(90)90057-Z

10.1111/j.2042-7158.1990.tb05412.x

10.1016/S0278-6915(00)00039-9

10.1006/phrs.1999.0648

Farombi EO, 2001, Inhibition of aflatoxin B1‐induced clastogenicity and hepatocarcinogenicity by kolaviron (Garcinia biflavanones) in rats, Mutat. Res., 483, S106

10.1006/phrs.2001.0907

10.1076/phbi.40.2.107.5838

Farombi EO, 2003, Molecular, Therapeutic Aspects of Redox Biochemistry., 207

10.1097/00008469-200010000-00010

10.1093/ajcn/71.5.1103

10.1111/j.1365-2621.1995.tb05668.x

10.1016/S0076-6879(78)52032-6

10.1016/0003-2697(92)90122-N

10.1016/S0022-2275(20)37249-7

10.1016/S0308-8146(98)00239-8

10.1016/S0891-5849(02)00847-X

10.1111/j.1745-4522.1996.tb00065.x

10.1016/S0140-6736(94)92211-X

10.1002/(SICI)1097-0010(200004)80:5<561::AID-JSFA574>3.0.CO;2-#

10.1016/S0308-8146(95)00254-5

10.1002/1097-0010(200007)80:9<1307::AID-JSFA638>3.0.CO;2-P

10.1038/sj.ejcn.1600540

10.1161/01.ATV.18.5.833

10.1046/j.1525-1373.1999.d01-34.x

10.1080/10408399509527689

Farombi EO, 2004, Ex vivo and in vitro protective effects of kolaviron against oxygen‐derived radical‐induced DNA damage and oxidative stress in human lymphocytes and rat liver cells, Cell Biol. Toxicol., 20, 1315

Pekkarinen SG, 1999, Flavonoids quercetin, myricetin, kaempferol and (+)‐catechin as antioxidants in methyl linolealate, J. Sci. Food Agric., 80, 985

10.1016/S0308-8146(83)80001-6

10.1016/0955-2863(95)00168-9

Iwu MM, 1986, Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure–Activity Relationships., 485

Thông tin
Thông tin xuất bản

Clinical and Experimental Pharmacology and Physiology

Tập 32 Số 8

667-674

Thông tin tác giả