Antioxidative Capacity Of Irbesartan

Cardiovascular disease as a common disease is becoming one of the common causes of death in china. Some literature reported oxidative stress played an important role in many diseases,such as atherosclerosis, hypertension, heart failure and atrial fibrillation. Antioxidants are able to inhibit the development of oxidative stress. Irbesartan[2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)·phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one] is an angiotensin receptor blocker, which has been widely used in the treatment of hypertension, coronary heart disease, and inhibits cardiac remodeling. There have been little reported adout the therapeutic effects of irbesartan to inhibit the oxidative stress. The purpose of this paper is to investigate the antioxidant effect of irbesartan by in vivo and in vitro to provide the basis for irbesartan in clinical application.Methods:1. In vivo:16 adult Wistar rats[(170±10) g] were prepared(8 females and 8 males). The rats were divided into two groups at random:Compared group(n=8):fed with distilled water by intragastric administration every day. Irbesartan group(n=8):fed with irbesartan(15mg·kg-1·d-1) by intragastric administration every day.0.5 mL blood of tail's vein was culled respectively at the 7th day, the 14th day, the 21st day and the 28th day. The GSH-Px, SOD and CAT activities and content of MDA were tested by the means of spectrophotometry. The rats'blood and livers were taken out at the 28th day. And then liver tissue homogenate with a percentage of 10% was made by PBS in ice bath. The activities of GSH-Px, SOD, CAT and MDA content of the liver tissue homogenate were tested by the means of spectrophotometry.2. In vitro:Investigat the antioxidant effect of irbesartan by the oxidized erythrocytes induced by AAPH and H2O2. And test the capacity of irbesartan to scavenge ABTS+. All the methods are chemical systems and chemical simulation of biological systems.Result:1. In vivo:the normal rats were intragastriced administration for 28d, the result is that the activity of the GSH-Px and CAT all increased as the extended drug time compared to the matched group, particularly on the 28d the statistical significance is obvious(P< 0.001). On the 7d the activity of the SOD decreased, while increased compared with the matched group after two weeks. So it do not have obvious statistical significance. In the 28d the MDA content all decreased obviously compared with the matched group, especially at the 21 d and the 28d the statistical significance is obvious(P< 0.005). After intragastricing administration 28, the activity of the GSH-Px SOD and CAT increased obviously, while the MDA content decreased obviously(P< 0.005).2. In vitro:(1) Irbesartan is a good scavenger for ABTS+(2) In the erythrocyte hemolysis system induced by the AAPH, Irbesartan can clear free radical. But compare with the Trolox and VC, the irbsartan can clean out less in the same concentration.(3) In the low concentration, the irbesartan is weaker effect in inhibiting erythrocyte hemolysis induced by the H2O2, comparing with the standard antioxygen. But when the concentration is 70μM, the irbesartan is stronger than the standard antioxygen VC, but weaker than Trolox.Conclusion:Irbesartan can significantly delay the oxidative stress of normal rats by enhancing the activity of GSH-Px, CAT,SOD and reducing the content of MDA significantly in normal rat blood and liver. And it is also a strong scavenger of ABTS+·. It can effectively inhibit the hemolysis of human blood which is induced by AAPH and H2O2.