Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. Methods: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B 6 and B 12 , folate, interleukin (IL)-12, tumour necrosis factor (TNF)-a, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). Results: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) mmol/l) than in controls (10.1 (2.5) mmol/l; p,0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B 6 , vitamin B 12 , and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-a, leukocyte nitric oxide production, or plasma diene conjugate levels. Conclusions: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B 6 , vitamin B 12 , or folate.
Oxidative stress occurs in progressive as well as benign MS. The finding that cells withstand oxidative stress, due to upregulated cellular antioxidant defence mechanisms, suggests that reactive oxygen species (ROS) formation in MS is not necessarily deleterious.
From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melatonin did not significantly influence food consumption, but it did increase the body weight of older mice; it did not influence physical strength or the presence of fatigue; it decreased locomotor activity and body temperature; it inhibited free radical processes in serum, brain, and liver; it slowed down the age-related switching-off of estrous function; and it increased life span. However, we also found that treatment with the used dose of melatonin increased spontaneous tumor incidence in mice. For this reason, we concluded that it would be premature to recommend melatonin as a geroprotector for long-term use.
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