S-Adenosylmethionine Prevents Oxidative Stress and Modulates Glutathione Metabolism in TgCRND8 Mice Fed a B-Vitamin Deficient Diet

Abstract

Oxidative stress, altered glutathione levels, and hyperhomocysteinemia play critical roles in Alzheimer's disease. We studied the relationships between hyperhomocysteinemia, glutathione, and oxidative stress in TgCRND8 mice maintained in conditions of folate, B12, and B6 deficiency and the effect of S-adenosylmethionine supplementation. We found that hyperhomocysteinemia was correlated with increased reduced/oxidized brain glutathione ratio, with decreased glutathione S-transferase activity and increased lipid peroxidation. S-adenosylmethionine potentiated superoxide dismutase and glutathione S-transferase activity and restored altered brain glutathione and erythrocytes lipid peroxidation. These results underline the importance of S-adenosylmethionine as neuroprotective compound, acting both on methylation and oxidation metabolism.

Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats

“…Hence, it was of interest to know the effect of SAM on cognitive impairments due to epilepsy. S-adenosyl methionine also has shown antioxidant effects on rat brain tissue [13]. But the role of the antioxidant effect of SAM on improving learning and memory in epilepsy has not been studied.…”

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

“…Downregulation of MAT2A might correspond to a compensatory effect of stressed neurons in order to ensure high levels of SAM for sufficient neurotransmitter generation. On the other hand, low SAM levels resulting from a deregulation of the cellular methylation machinery might evoke cellular stress, and an association between SAM and the superoxide dismutase activity was reported recently (43). Additionally, the down-regulation of PRDX4 was suggested to facilitate cell death (44).…”

Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

“…The epidemiologic studies support a positive association between the plasma homocysteine concentrations and CAD risk. Hyperhomocysteinemia resulting from aberrations in one-carbon metabolism was demonstrated to increase superoxide anion production by multiple mechanisms [40], includes: (i) inhibition of the activity of cellular antioxidant enzymes such as cellular glutathione peroxidase or hemeoxygenase-1, (ii) homocysteine autooxidation, (iii) NOS-dependent generation of superoxide anion (O 2 -• ) via uncoupling of eNOS, (iv) decrease of extracellular superoxide dismutase activity and (v) by phosphorylation at p47 phox and p67 phox subunits of NADPH oxidase, thereby stimulating superoxide generation [39]. A study found that plasma homocysteine concentration and SNPs in the enzyme MTHFR were not significantly associated with carotid IMT [33].…”