Naslov
Effects of iron-induced lipid peroxIdation on the experimental autoimmune encephalomyelitis in rats

Autori
Ćurko-Cofek, Božena ; Grubić-Kezele, Tanja ; Tota, Marin ; Marinić, Jelena ; Starčević-Čizmarević, Nada ; Milin, Čedomila ; Radošević-Stašić, Biserka ; Barac-Latas, Vesna.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Polić, Bojan - Krk : The Croatian Immunological Society, 2014, 61-61

Skup
Godišnji skup Hrvatskog imunološkog društva

Mjesto i datum
Hrvatska, 17.10.2014. - 18.10.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
EAE; iron-induced lipid peroxIdation; brain; spinal cord; liver

Sažetak
Background: Iron is an essential trophic factor that plays a key role in vital cell functions. It is indispensable cofactor for enzymes involved in cell proliferation, respiration, folate metabolism and DNA synthesis, having a crucial role in metabolic pathways involved in electron transfer and ATP production. The redox potential of Fe2+/Fe3+ favors its use in a number of protein complexes, but as a part of the Fenton reaction ferrous iron may also catalyze the conversion of hydrogen peroxide to highly reactive hydroxyl radicals that damage DNA, proteins and lipids. Therefore, the maintenance of iron homeostasis in the body and in the cells must be balanced, to ensure enough iron for the metabolism, but to avoid excessive, toxic levels of iron that provoke oxidative tissue injuries. Since the regulation of iron homeostasis is a prerequisite also for normal neurological function, in this study we analyzed the effects of iron overload on the lipid peroxidation processes (LP) in tissues and on kinetics of experimental autoimmune encephalomyelitis (EAE) in female DA rats. Material and methods: Female Dark Agouti (DA) rats, aged 2-3 months, were immunized by subcutaneous injection of bovine brain white matter homogenate (BBH) in complete Freund’s adjuvant (CFA). Animals were then subdivided into: 1) iron treated and 2) saline treated group. Experimental group consisted of iron overloaded rats, treated by intraperitoneal injections of iron sucrose (Venofer) at the dose of 75 mg/kg bw (6 times/week) for two consecutive weeks, before the immunization of rats. Control group consisted of rats treated by an equivalent volume of sterile saline. The severity of disease was clinically assessed by standard criteria (0-4). Animals were sacrificed by exsanguinations on day 13th after the active induction of disease. Tissue concentrations of Fe2+ and LP in the brain, spinal cord and liver were determined by PHILIPS PU 7000-ICP spectrometer (method ASTM D 19756-91 at a fixed wavelength of 259.940 nm) and by estimation of malondialdehyde (MDA) concentration (nmol/mg of tissue weight) based on the reaction with the thiobarbituric acid, respectively. Differences between groups were assessed by Mann-Whitney U test. Results: The data showed that iron overload markedly augmented the tissue concentration of iron in the brain and spinal cord, as well as in the liver (p<0, 001 in comparison with saline treated rats). This was followed by high upregulation of lipid peroxidation in the brain and in the liver, suggesting that excess of iron has increased the oxidative and nitrative stress, catalysing the generation of highly reactive hydroxyl, alkoxyl and peroxyl radicals from hydrogen and lipid peroxides. Simultaneously, iron overload changed also the kinetics of EAE, leading to faster appearance of clinical symptoms of EAE, to translocation of the firt peak of disease from 17th to 12th day and appearence of a new relaps on the 21st postimmunization day (p<0.05). Conclusions: The data point to damaging effects of iron overload-induced lipid peroxidation in the brain and in the liver, emphasizing a high influence of local and peripheral iron-regulating mechanisms on the pathogenesis of autoimmune demyelinating diseases, such as EAE and multiple sclerosis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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