Sex Difference in Oxidative Stress Parameters in Spinal Cord of Rats with Experimental Autoimmune Encephalomyelitis: Relation to Neurological Deficit

Abstract

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 O concentration increased only in spinal cord of male rats. Consequently, SOD activity was lower, whereas O 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.

The Evaluation of Oxidative Stress Parameters in Serum Patients with Relapsing‐Remitting Multiple Sclerosis Treated with II‐Line Immunomodulatory Therapy

“…Moreover, it was associated with an increase in MDA level in the spinal cord. With EAE development, superoxide dismutase (SOD) activity decreased, while O2 concentration, XO activity, and iNOS mRNA expression increased only in the spinal cord of male rats which exhibited more severe neurological symptoms compared to the female rats [ 63 ].…”

Experimental autoimmune encephalomyelitis from a tissue energy perspective

“…ROS/RNS are routinely produced under physiological conditions; however, they normally pose very little threat because of a specialised set of endogenous defence and repair mechanisms. The CNS anti-oxidant defence system is composed of non-enzymatic (for example, glutathione [GSH] and uric acid) and enzymatic (for example, superoxide dismutases, GSH peroxidase, catalase, haeme-oxygenases, quinone oxidoreductases and peroxiredoxins) anti-oxidants 74 , 75 . During pathological conditions, such as inflammation, the overproduction of ROS/RNS overwhelms this anti-oxidant system, resulting in oxidative/nitrative stress.…”

“…Besides changes in NOX activity, alterations in other mediators of oxidative stress have been revealed in EAE. Two independent groups have reported reduced GSH levels in rodents with clinical EAE 75 , 83 . Morales Pantoja et al .…”

Therapeutic potential of agmatine in the experimental autoimmune encephalomyelitis

“…Suppressed NO • metabolism seems to express beneficial effects during the course of experimental MS 11 . Malondialdehyde (MDA) is an end-product of polyunsaturated fatty acids peroxidation and represents the severity of oxidative stress-induced brain injury 12 . An indicator of LPO was determined by measurable parameter thiobarbituric acid reactive substances (TBARS) 13 .…”