Wednesday, March 10, 2010

You Anti-Oxidants are trying to Kill You

Maybe we lack uricase because we developed in a high ROS environment?

Birds lack uricase, and are also high-energy producers. Exercise increases oxidation of uric acid to allantoin. Not enough to keep uric acid from being high in the urine, but maybe enough to interfere with crystal formation?

These guys compare allantoin to vitamin c. I don't have access to the article, but just the preview itself is interesting.

The similarity of energy characteristics of reactions of hydroxylation of allantoin and vitamin C should determine the similarity of their biological effects in model systems in vitro and in vivo. In view of this, we performed comparative evaluation of the ability of allantoin, ascorbic acid, and p-aminobenzoic acid (PABA) to quench free-radical processes and inactivate genotoxicity of hydrogen peroxide."

I wonder if this stuff shortens the lives of glucose-blocked nematode worms? And whether uric acid would have the same effect, or not.

Wikipedia on allantoin;

Manufacturers cite several beneficial effects for allantoin as an active ingredient in over-the-counter cosmetics: a moisturizing and keratolytic effect, increasing the water content of the extracellular matrix and enhancing the desquamation of upper layers of dead skin cells, increasing the smoothness of the skin; promotion of cell proliferation and wound healing

That worm study did mention something about collagen... Calorie restricted mice live longer (the ones that don't die younger, anyways) and heal slower.

Uric acid as a precursor for allantoin, allantoin perhaps a tool in the repair kit. Uric acid increases blood pressure.

"Interestingly, raising uric acid levels in rats resulted in increased BP and the development of microvascular disease (resembling arteriolosclerosis) in the kidneys.17-18 The mechanism of hypertension was shown to be caused by a uric acid–mediated reduction in endothelial nitric oxide levels19-20 and stimulation of renin expression.18 Studies in humans have also correlated uric acid levels with both endothelial dysfunction21-22 and elevated plasma renin activity"

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism

The previous experiments were performed under low-salt-diet conditions, because the effect of hyperuricemia on blood pressure is most pronounced under these dietary conditions

Huh. In this study, they show uric acid as increasing smooth muscle cell proliferation in isolated cells from rats. Uric acid levels were increased by adding uric acid in this part of the study. I wonder if any of it oxidized? (Rhetorical question. Of course it did.

Then they show arteriosclerosis in rat kidneys. The rat's uric acid levels are increased by blocking the oxidation of uric acid. They don't show what happens to the elevated uric acid once it reaches the kidney. The kidney would be a major site for uric acid oxidation, which is also allantoin synthesis. How come the elevated uric acid levels didn't cause arteriosclerosis outside of the kidneys?

Maybe an unresolved healing process could lead to an elevation of uric acid, and high blood pressure?

Taking lots of anti-oxidants to prevent oxidative stress might not be a good idea if you depend on reactive oxygen species formation to oxidize uric acid into allantoin to somehow facilitate smooth muscle proliferation and arterial healing.

Most of this post came from some comments I made at Peter's blog (Hyperlipid.) It's what led me to make yesterdays post, and it sort of leads in to the next post, so I thought I'd work it in here.


donny said...

Of course the uric acid levels were more concentrated in the kidney. Duh.

Uric Salt said...

You Anti-Oxidants are trying to Kill You · Your Sialic Acid is Trying to Kill You · Pre-inflammatory? Glutamic acid and bones · Is saturated fat ...