Comparison of uric acid and ascorbic acid in protection against EAE

Area of Science:

• Biochemistry
• Evolutionary Biology
• Neuroimmunology

Background:

• Serum uric acid (UA) levels rose in hominids, coinciding with the loss of ascorbic acid (AA) synthesis in higher mammals.
• UA is proposed to have replaced AA as a primary antioxidant.
• Ascorbic acid (AA) does not prevent experimental allergic encephalomyelitis (EAE), a disease linked to peroxynitrite (ONOO-) activity, while UA does.

Purpose of the Study:

• To compare the antioxidant capacities of uric acid (UA) and ascorbic acid (AA) in vitro and in vivo.
• To investigate the role of iron ions in the differential antioxidant effects of UA and AA against peroxynitrite (ONOO-).
• To elucidate the mechanisms behind UA's protective effects in experimental allergic encephalomyelitis (EAE).

Main Methods:

• In vitro comparison of UA and AA's ability to inhibit peroxynitrite (ONOO-) nitration and oxidation.
• Assessment of UA and AA's efficacy in preventing dihydrorhodamine-123 oxidation in the presence of Fe3+.
• In vivo and in vitro evaluation of AA's effect on lipid peroxidation.

Main Results:

• UA and AA exhibited similar efficacy in inhibiting ONOO- nitration.
• UA demonstrated superior ability to prevent ONOO- mediated oxidation, especially in the presence of Fe3+.
• Ascorbic acid (AA) potentiated lipid peroxidation both in vivo and in vitro.

Conclusions:

• Uric acid (UA) offers superior protection against ONOO- mediated oxidative damage compared to ascorbic acid (AA), particularly in the presence of iron ions.
• UA's enhanced ability to neutralize ONOO- in the presence of iron may explain its protective effects in EAE.
• The findings suggest a distinct and potentially more critical role for UA as an antioxidant in specific biological contexts.