Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit.
The study examined (a) whether there is sex difference in spinal cord and plasma oxidative stress profiles in Dark Agouti rats immunised for experimental autoimmune encephalomyelitis (EAE), the principal experimental model of multiple sclerosis, and (b) whether there is correlation between the oxidative stress in spinal cord and neurological deficit. Regardless of rat sex, with the disease development xanthine oxidase (XO) activity and inducible nitric oxide synthase (iNOS) mRNA expression increased in spinal cord, whereas glutathione levels decreased. This was accompanied by the rise in spinal cord malondialdehyde level. On the other hand, with EAE development superoxide dismutase (SOD) activity decreased, while O2-concentration increased only in spinal cord of male rats. Consequently, SOD activity was lower, whereas O2-concentration was higher in spinal cord of male rats with clinically manifested EAE. XO activity and iNOS mRNA expression were also elevated in their spinal cord. Consistently, in the effector phase of EAE the concentration of advanced oxidation protein product (AOPP) was higher in spinal cord of male rats, which exhibit more severe neurological deficit than their female counterparts. In as much as data obtained in the experimental models could be translated to humans, the findings may be relevant for designing sex-specific antioxidant therapeutic strategies. Furthermore, the study indicated that the increased pro-oxidant-antioxidant balance in plasma may be an early indicator of EAE development. Moreover, it showed that plasma AOPP level may indicate not only actual activity of the disease, but also serve to predict severity of its course.
Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Bulevar despota Stefana 142, 11060, Belgrade, Serbia. mirjana.dimitrijevic@ibiss.bg.ac.rs.
Mirjana
M
Dimitrijević
Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221, Belgrade, Serbia.
Jelena
J
Kotur-Stevuljević
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221, Belgrade, Serbia.
Zorica
Z
Stojić-Vukanić
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221, Belgrade, Serbia.
Ivana
I
Vujnović
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221, Belgrade, Serbia.
Ivan
I
Pilipović
Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221, Belgrade, Serbia.
Mirjana
M
Nacka-Aleksić
Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221, Belgrade, Serbia.
Gordana
G
Leposavić
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D008297:Male; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D012727:Sex Characteristics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
Experimental autoimmune encephalomyelitis; Multiple sclerosis; Oxidative stress; Rat; Sex differences; Spinal cord