Tài liệu Báo cáo khoa học: Oxidative stress in the hippocampus after pilocarpineinduced status

Oxidative stress in the hippocampus after pilocarpine￾induced status epilepticus in Wistar rats

Rivelilson M. Freitas, Silvaˆnia M. M. Vasconcelos, Francisca C. F. Souza, Glauce S. B. Viana

and Marta M. F. Fonteles

Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, School of Medicine, Federal University of Ceara´, Fortaleza,

Brazil

Status epilepticus (SE) is a neurological emergency

with an associated mortality of 10–12% [1]. Pilocar￾pine-induced seizure models have provided information

on the behavioral and neurochemical characteristics

associated with seizure activity [2,3]. Other studies sug￾gest permanent changes in different biochemical sys￾tems during SE. An increase in lipid peroxidation, a

decrease in GSH content, and excessive free radical

formation may occur during SE induced by pilocarpine

[4,5].

This model can be used to investigate the develop￾ment of neuropathology in SE [6]. Despite numerous

studies clearly indicating the importance of enzyme

activity in the epileptic phenomenon, the mechanisms

by which these enzymes influence SE are not com￾pletely understood [7,8]. Therefore, we decided to

study enzymatic activity related to oxidative stress

mechanisms during SE [9].

Oxidative stress, which is defined as the over-produc￾tion of free radicals, can dramatically alter neuronal

function and has been related to SE [10,11]. It is partic￾ularly facilitated in the brain, as the brain contains

large quantities of oxidizable lipids and metals, and,

moreover, has fewer antioxidant mechanisms than

other tissues [8].

Free radicals are chemical entities characterized by an

orbital containing an unpaired electron [12]. This elec￾tron confers on these molecules a strong propensity to

react with target molecules by giving or withdrawing

one electron from the target molecules to complete their

own orbital [13]. Superoxide, a free radical, can be gen￾erated in the brain by several mechanisms such as

Keywords

hippocampus; oxidative stress; pilocarpine;

seizures; status epilepticus

Correspondence

R. M. Freitas, Rua Frederico Severo 201,

Ap 103, Bl 07, Messejana, Fortaleza,

60830-310, Brazil

Tel ⁄ Fax: +55 85 3274 6091

E-mail: [email protected]

(Received 23 October 2004, revised 28

November 2004, accepted 20 December

2004)

doi:10.1111/j.1742-4658.2004.04537.x

The role of oxidative stress in pilocarpine-induced status epilepticus was

investigated by measuring lipid peroxidation level, nitrite content, GSH con￾centration, and superoxide dismutase and catalase activities in the hippo￾campus of Wistar rats. The control group was subcutaneously injected with

0.9% saline. The experimental group received pilocarpine (400 mgÆkg)1

,

subcutaneous). Both groups were killed 24 h after treatment. After the

induction of status epilepticus, there were significant increases (77% and

51%, respectively) in lipid peroxidation and nitrite concentration, but a

55% decrease in GSH content. Catalase activity was augmented 88%, but

superoxide dismutase activity remained unaltered. These results show evi￾dence of neuronal damage in the hippocampus due to a decrease in GSH

concentration and an increase in lipid peroxidation and nitrite content.

GSH and catalase activity are involved in mechanisms responsible for elim￾inating oxygen free radicals during the establishment of status epilepticus in

the hippocampus. In contrast, no correlations between superoxide dismutase

and catalase activities were observed. Our results suggest that GSH and

catalase activity play an antioxidant role in the hippocampus during status

epilepticus.

Abbreviations

ROS, reactive oxygen species; SE, status elipticus.

FEBS Journal 272 (2005) 1307–1312 ª 2005 FEBS 1307