PlASMA MAlONDIAlDEHYDE AND CATAlASE lEVElS ...

JOURNAL OF ANKARA MEDICAL SCHOOL

Vol 20, No 4,1998

19'1-193

PlASMA MAlONDIAlDEHYDE AND CATAlASE lEVElS BEFORE AND AFTER ElECTROCONVUlSIVE THERAPY*

Engin Tutkun**

• ismail Akinci**

• Tülin Söylemezoglu**

Aykut Özden**

• Hakan Kumbasar**

• Hüseyin Özsan**

SUMMARY

Molecules that serve in biologic systems as elecu'on acceptor are referred to as "oxidants" or "free radicals". Oxidative stress can be considered as a disturbance in the pro-oxidant - antioxidant balance in t~lvorof the pro-oxidant.. Malondialdehyde (MDA) is a c1eavage product of fatty acid peroxidatiol1. The antioxidant defence is largely provided by overall enzvmes (e.g. superoxide dismutase, glutathione peroxidase, catalase, glucose-6- phosphate dehydrogenase ete.) which tend to neutralize the oxidants (°1-, superoxide anion; H0l' perhydroxyl radical; H101' hydrogen peroxide; OH-, hydroxyl radical etc). In order to evaluate the effect of electroconvulsive therapy (ECT)on antimddant enzyme status and lipid peroxidation, we measLIred the levels of MDA and activities of catalase in 75 patients before and after ECT. MDA levels decreased and catalase le ve Is increased significantly atter ECT. We concluded that ECT shows antioxidant activity with an unknown mechanism. Key

Words: Catalase, Electroconvulsive therapy, Malondialdehyde

Free radicals are chemical species possessing an unpaired electron that can be considered as fragments of inolecides and which are generally very active (1). Toxic free raclicals can be produced by niany reactions requirecl for the niaintenance of nornial metabolisni and the production of energy in celI (2). Generation of free radicals in biological systenis is niostly the result of radiolysis, photolysis, thernial c1egradation of organic niaterial and redox reactions catalyzed by nietal ions and enzynies (3). Polyunsaturated fatty acids are particularly vulnarable to free raclical attaek. This oxidative dainage is ternieellipid peroxidation anel causes aredurtion in menibrane fluidity and pernieability. Free radical induced daniage to proteins niay result in fragnientation, cross-linking, aggregation of protein (4). Strand scission, destruction and fragnientation of bases and eleoxyribose sugars have all been reported to occur following free radical (niainly hydroxyl) attack on DNA. The resulting cytotoxicity, niutations and patential for nialignant change occurs as a result of induced chroniosonial aberratians (5). Much of evidence is based on experiniental data indicating increased rates of lipid peroxidation in diseased tissues, • Presented at the 6 th World ••

Received:

Department Department February

Congress of Biological

evaiuation of therapeutic proceclures, ameliarating effect of antiox iclants, ete. The niechanisni underlying therapeutic effect of ECT is stili unknown (6). Althaugh niost effects of ECT ha"e been investigated, we were unable to fincl any documentation including the effect of ECT on lipid peroxidation. The priniary aini of this study was to evaluate the effect of single-dose ECT on i ipiel peroxidation and antioxid,c,ipt enzynie status. MATERIALS AND

15 schizophrenic patients, without another chronic systeniic disturbance, hospitalizeel on the inpatient psychiatry department of Medical Faculty of Ankara University who were planned to underga ECT were chosen for the study. As is generally the case, failure to respond to the other therapeutic procedures and development of intolerable side effects of drugs were niajor reasons for patients' being referred for ECT. Each patient gave written information for participation in the study. Although the planned course of ECT treatnients rangecl froni 4 to 12 sessions over an 8 to 32 day

Psychiatry June 22-27,

of Toxicology, Institute of Forensic Medicine, University of Psychiatry, Medical Faculty of Ankara University

ll,

1998

Accepted:

June 24,1998

METHODS

1997 Nice, France

of Ankara

192

PLASMA

MALONDIALDEHYDE

AND

CATALASE

LEVELS

period, blood samples were drawn before and aftei' the first ECT. All patients reeeived eonventional bilateral ECT with bifrontotemporal eleetrode plaeement Mean age was 43,6 ranging from 21 to 52. Venous blood samples were drawn from a peripheral vein at the beginning and 5 minutes after the first ECT session between 7 to 9 am. for the determination of MDA and eatalase, The eatalase mediated deeomposition of H202 was followed directiyat 240 nm. The results were ealeulated from the extinetion coeffieient of H202 at 240 nm., speetrophotometrieally (7). The thiobarbiturie acid (TBA) assay is the most popular and easiest method used as an indieator of lipid pemxidation and free radical aetivity in biologieal samples. The assay is based upon the reaetion of TBA with MDA, one of the aldehyde pmduets of lipid pemxidation (8).' RESULTS

Fifteen patients (11 women and 4 men) partieipated in the study. As mentioned before, all blood samples were taken before and 5 minutes after the first ECT. The resuIts of patients before ECT and the comparison of results before and after ECT were given at Table-l . MDA levels deereased and eatalase levels increased signifieantly after ECT. The statistieal analyses were made with 'paired t-test'. The differenees between the groups were statisti-eally meaningful. DISCUSSION

Pathologie dysfunetions suggested to involve oxygen radieals inelude eonditions affecting severalorgan systems like inflammatory-immune injury (e.g. glomerulonephritis, vaseulitis) (9), isehemia-reflow injury

BEFORE

AND

AFTER

ELECTROCONVULSiVE

THERAPY

Table 1. Plasma MDA and eatalase levels in Pre- and Post-ECT patient

n=15 for all

groups. MDA

Pre-ECT Post-ECT Paired t test

(nmol;

mL)

Catalase (c;

gHb.)

77.5 ± 9.2

8.1 ± 1.3

4.7 ± 1.1 p < 0.001

125.2±21.3 p < 0.001

(10), drug and toxin indueed reaetions (11), aleohol, radiation injury, iron overload (12), aging and eaneer (13), lungs (e.g. eigarette smoking) (14), heart and eardiovaseular system (e.g. Doxorubiein toxieity), kidney (e.g. renal graft rejeetion) (15), brain (e.g. hyperbarie oxygen) (16,17). In the light of this infomiation, we can easily understand that lipid peroxidation and antioxidant defense systems play an important role in the meehanism of many pathologie events of body, like in CNS (18).

In our study, we aimed to ObSei-V2 the effeet of ECT on lipid peroxidation (MDA) and antioxidant defense systems (eatalase). As a result, we observed a meaningful alteration in eatalase and MDA, between preand post-ECT groups. There was an increase in eatalase (with a ratio of % 61) and a deerease in MDA (with a i'atio of %58). We eonelude that,ECT prevents lipid peroxidation and free radical damage and strengthens antioxidant defense systems of the body. Probably, such studies mav lead to new approaehes in therapeutie meehanism of ECT and underlying etiology of mental disorders. Stili, these initial observations need to be eonfirmed in a large number of subjeets with advaneed'teehniques those have the ability to evaluate, even minor brain changes. Further investigations should alsa involve longterm follow-up studies and animal experiments those give the clianee to dii'eetly observe the target tissue.

REFERENCES 1.

Davies KJA, Goldberg AL. Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cell. J Biol Chem 1987; 262/17:8227-8234

2.

Bosaga HS. Biochemical aspects of free radicals. Cell Biol 1990; 68:989-998

3.

Cochrane CG. Cellular injury by oxidants. Ani J Med 91 (suppI.3C): 235-305 Clark RA, Stone PJ, Hag AE, Calore JO, Franzblau C. Myeloperoxidase catalysed in activation of alpha-l-protease

4.

inhibitor 348-53 5.

by human neutrophils.

Aruoma OL, Halliwell ion-dependent

B, Gajewski

ce of hydrogen 604

M . .copper

damage to bases in DNA in the presen-

Biol Chem

1991; 273: 601-

6.

Milstein V, Smail JG, Miller, MJ, Sharpley PH, Smail IV. Mechanisms of action of ECT: Schizophrenia and schizo-affective disorder. Biol Psychiatry 1992; 27:12821292

7.

Grankvist

8.

and scavengers of hydroxyl radicals protect against the toxic action of alloxan on pancreatic islets cells in vitro. Biochem J 1979;182: 17-25 Esterbaur H, Cheeseman K. Determination of aldehydic li-

Biochem

Biol Chem 198,1; 256: E, Dizdaroglu

peroxide.

K,Marklund

pid peroxidation hydroxynonenal.

S. Superoxide

dismutase,

catalase

products: malondi-aldehyde and 4Methods Enzymol. 1990; 186 :407 -421

193

Engin Tutkun, ismail Akinei, Hilin Söylemezoglu, Hakan Kumbasar, Aykut Özden, HÜseyin Özsan

9.

Chaudri G, Clark lA, Hunt NH, Cowden WB, Ceredig R. Effect of antioxidants on priniary alloantigen-induced Tcell activation and proliferation. J Immunol 1986; 137: 2646-52

10. Becker LC, Anibrossia G. Myocardial conseqences of reperfusion. Prog In Cardiovasc Dis 1987; 30/1 :23-44 11. Garcia-Escrig M, Martinez J, Fernandez-Ponsati J, Diaz L, 50to O. Severe central nervous system toxicity af ter chronic treatnient with cyclosporine. Clin Neuro-pharni 1994; 17/3 :298-302 12. Dillard

Cl, Downey

lipid peroxidation 19:127-33

JE, Tappel AL. Effect of antioxi in

iron

loaded

rats.

dants on

Lipid

1984;

13. Ames BN. Dietary carcinogens and anticarcinogens: oxygen radicals and degenerative r1iseases. Science 1983; 221:1256-64 14. Brighani J