Dimethyl Sulfoxide and Ebselen Prevent Convulsions Induced by 5-Aminolevulinic Acid

Neurochemical Research, Vol. 29, No. 10, October 2004 ( 2004), pp. 17931800Dimethyl Sulfoxide and Ebselen Prevent Convulsions

Induced by 5-Aminolevulinic AcidCarlos Andre Prauchner,1 Adriano Neujahr Agostini,2 Akemi Morimoto,2

Paula Rossini Augusti,2 Tas Cristina Unfer,2 Gilson Zeni,1 Carlos Fernando Mello,1

and Tatiana Emanuelli1,2,3(Accepted April 29, 2004)We investigated whether intrastriatal (i.s.) administration of 5-aminolevulinic acid (ALA)

induces oxidative damage and whether behavioral alterations induced by i.s. administration

of ALA could be aected by antioxidants. Unilateral injection of ALA (6 lmol/striatum)

increased (30%) thiobarbituric acid-reactive substances (TBARS), but did not aect striatal content of total thiol groups. ALA-induced body asymmetry was not prevented by pretreatment with ascorbic acid (100 mg/kg, s.c.), dimethyl sulfoxide (DMSO, 0.5 ll/striatum,i.s.) or ebselen (10 nmol/striatum, i.s.). ALA-induced convulsions were not prevented by

ascorbic acid, but were partially prevented by DMSO and completely prevented by ebselen.

Ebselen completely prevented the increase of striatal TBARS induced by ALA. Results

obtained suggest the involvement of reactive species in ALA-induced convulsions and may

be of value in understanding the physiopathology of neurological dysfunctions associated

to ALA overload.KEY WORDS: 5-Aminolevulinic acid; antioxidants; body asymmetry; convulsions; oxidative damage.INTRODUCTION5-Aminolevulinic acid (ALA) is an haem precursor that accumulates in tissues of patients suering from acute intermittent porphyria (AIP),

tyrosinosis or lead poisoning, due to a deciency in

the haem biosynthetic pathway (13). Such disorders are characterized by acute attacks that start

with abdominal pain (peripheral neuropathy) and

may be accompanied by disturbances in central nervous system (anxiety, psychosis, insomnia, disturbed

consciousness and seizures) (1,3). The pathogenesis

of these manifestations is not completely elucidated

but a signicant amount of evidence suggests the

direct involvement of ALA (1,4,5). Other conditions

that may result in ALA overload in the central nervous system include the use of ALA or ALA-esters

as photosensitizers in photodynamic therapy of

human gliomas (6) and the oral administration of

ALA that has been clinically used to delineate

malignant gliomas (7).We have recently demonstrated that the intrastriatal administration of ALA induces convulsions

and body asymmetry in rats (8). Such behavioral

alterations were prevented by 6,7-dinitroquinoxa-

line-2,3-dione (DNQX), suggesting the involvement1 Curso de Pos-Graduacao em Bioqumica Toxicologica, Centrode Ciencias Naturais e Exatas, Universidade Federal de SantaMaria, Santa Maria, RS, 97105-900, Brasil.2 NIDAL, Departamento de Tecnologia e Ciencia dos Alimentos,Centro de Ciencias Rurais,...