engleski

Iron overload induces gender-dependent changes in lipid peroxidation and in clinical course of experimental autoimmune encephalomyelits in rats

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 and induce the generation of secondary lipid products that damage DNA, proteins and lipids. To analyze the mechanisms possibly involved in pathogenesis of multiple sclerosis (MS) in this study we evaluated the effects of iron overload (IO) on iron status and lipid peroxidation processes (LPO) in tissues of female and male DA rats during EAE, a well-established MS animal model. Materials and methods: Female and male DA rats were treated by iron sucrose (75 mg/kg bw/day) or with saline solution during two weeks before the sensitization with bovine brain homogenate (BBH) in complete Freund's adjuvant (CFA). Clinical symptoms of EAE were evaluated during the 30 days. Serum and tissues of CNS and liver were sampled for determination of ferritin, iron, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) before immunization and during acute phase of EAE. The results were obtained by ELISA, ICP spectrometry and immunohistochemistry and analyzed by one way ANOVA and Kruscal Wallis tests. Results: In female EAE rats IO accelerated the onset of disease, while in male rats it accelerated second relapse and increased the mortality rate. During acute phase of EAE female IO rats sequestered more Fe in the liver, spinal cord and in the brain and produced more ferritin than male EAE rats. Male rats, however, reacted on IO by higher production of MDA or 4-HNE in the neural tissues and showed greater signs of plaque formation and gliosis in spinal cord. Conclusion: The data point to sexual dimorphism in mechanisms that regulate peripheral and brain iron homeostasis and imply that men and women during MS might be differentially vulnerable to exogenous iron overload.

Encephalomyelitis, Autoimmune, Experimental ; Iron Overload ; Lipid Peroxidation ; Multiple Sclerosis ; Sex

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