Zonisamide Inhibits Oxidative Stress Induced Lipid Peroxidation in Rat Brain Homogenate
Abstract number :
1.132
Submission category :
Year :
2000
Submission ID :
2634
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Akitane Mori, Takao Kaneyuki, Yasuko Noda, Lester Packer, Univ of CA, Berkeley, CA, U.S.A.; Okayama Prefectural Univ, Soja, Japan.
Rationale: It was shown recently by us that zonisamide (ZNS) scavenged hydroxyl and nitric oxide radicals in vitro in a dose dependent manner, and that ZNS reduced nitric oxide synthase activity, accelerated by NMDA with/without L-buthionine-[S,R]-sulfoxime pretreatment, to the control level in the hippocampus of rats. In this study, the antioxidant activity of ZNS was measured by assessing its inhibitory effects on lipid peroxidation of rat brain homogenates. Methods: Oxidative stress was induced with/without ZNS under following 2 kinds of condition: (1) homogenates in 20 mM Tris-HCl buffer pH 7.4 (1:10, w/v) and 5 mM H2O2 at 37 C for 60 min and (2) homogenates in saline (1:20, w/v) and 0.2 mM FeCl2-0.02 mM ascorbate at 37 C for 10 min. After incubation, the level of malonaldehyde plus 4-hydroxyalkenals was assayed in the supernatant as an index of lipid peroxidation, using LPO-586TM Kit. Results: ZNS reduced H2O2- and also FeCl2-ascorbate-induced lipid peroxidation in a dose dependent manner at concentrations ranging 1 to 10 mM; The 50% inhibiting concentration (IC50) of ZNS was 8.8 mM and 1.2 mM, respectively. Conclusion: These observations along with our previous findings suggest that ZNS could protect neurons from free radical damage which may lead to epileptogenic disorders