4 replies to this topic

[pkands]

from the calorierestriction.org list

Does resveratrol protect us from oxidation? The below paper is pdf-availed.

"Our studies demonstrate that RSV treatment ... may induce nephrotoxicity."





Elevation of oxidative-damage biomarkers during aging in F2 hybrid mice:

Protection by chronic oral intake of resveratrol.

Wong YT, Gruber J, Jenner AM, Ng MP, Ruan R, Tay FE.

Free Radic Biol Med. 2008 Dec 31. [Epub ahead of print]

PMID: 19159678



Abstract



Resveratrol (RSV), a naturally occurring phytoalexin that can be found in red wine, berries, and peanuts, has been shown to extend both mean and maximum life span in model organisms. RSV has also been reported to shift the physiology of middle-aged mice on a high-calorie diet toward that of mice on a standard diet. These beneficial effects of RSV have been suggested to resemble caloric restriction.



Our study in F2 four-way cross-hybrid mice was the first to evaluate the effects of aging and long-term RSV treatment (14.09±3.4 mg/L in drinking water for 6 or 12 months) on biomarkers of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OHdG); lipid, 8-iso-prostaglandin2alpha (8-iso-PGF2alpha); and protein, protein carbonyl content (PCC).



There was a significant age-dependent accumulation of oxidative damage to DNA, lipid, and protein as well as a clear increase in urine 8-iso-PGF2alpha levels in the majority of mouse tissues. Rates of age-dependent increases in damage biomarkers varied between tissues. Chronic RSV treatment elevated total RSV plasma levels and reduced the observed age-dependent accumulation of (1) 8OHdG in liver and heart, (2) 8-iso-PGF2alpha in heart and urine, and

(3) PCC in liver and kidney. However, a 12-month RSV intake resulted in significant elevation of 8-iso-PGF2alpha and PCC in kidney.



Our studies demonstrate that RSV treatment consistently attenuated oxidative damage in tissues where age-related oxidative damage accumulation was prominent, but also suggested that chronic RSV treatment may induce nephrotoxicity.

[maxwatt]

from the calorierestriction.org list

Does resveratrol protect us from oxidation? The below paper is pdf-availed.

"Our studies demonstrate that RSV treatment ... may induce nephrotoxicity."





Elevation of oxidative-damage biomarkers during aging in F2 hybrid mice:

Protection by chronic oral intake of resveratrol.

Wong YT, Gruber J, Jenner AM, Ng MP, Ruan R, Tay FE.

Free Radic Biol Med. 2008 Dec 31. [Epub ahead of print]

PMID: 19159678



Abstract



Resveratrol (RSV), a naturally occurring phytoalexin that can be found in red wine, berries, and peanuts, has been shown to extend both mean and maximum life span in model organisms. RSV has also been reported to shift the physiology of middle-aged mice on a high-calorie diet toward that of mice on a standard diet. These beneficial effects of RSV have been suggested to resemble caloric restriction.



Our study in F2 four-way cross-hybrid mice was the first to evaluate the effects of aging and long-term RSV treatment (14.09±3.4 mg/L in drinking water for 6 or 12 months) on biomarkers of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OHdG); lipid, 8-iso-prostaglandin2alpha (8-iso-PGF2alpha); and protein, protein carbonyl content (PCC).



There was a significant age-dependent accumulation of oxidative damage to DNA, lipid, and protein as well as a clear increase in urine 8-iso-PGF2alpha levels in the majority of mouse tissues. Rates of age-dependent increases in damage biomarkers varied between tissues. Chronic RSV treatment elevated total RSV plasma levels and reduced the observed age-dependent accumulation of (1) 8OHdG in liver and heart, (2) 8-iso-PGF2alpha in heart and urine, and

(3) PCC in liver and kidney. However, a 12-month RSV intake resulted in significant elevation of 8-iso-PGF2alpha and PCC in kidney.



Our studies demonstrate that RSV treatment consistently attenuated oxidative damage in tissues where age-related oxidative damage accumulation was prominent, but also suggested that chronic RSV treatment may induce nephrotoxicity.

Hard to tell what that means exactly, or to translate thestudy to anything like human subjects. Vitamin E and other vitamins have been found to result in a dose-dependent reduction in 8-iso-PGF2 excretion and decreased sensitivity of LDL to in vitro oxidation, which may prevent such possible damage.

[geddarkstorm]

What's really cool to me about this paper, is how they show resveratrol, especially resveratrol taken over 12 months, massively reduced DNA oxidative damage, especially in the heart and the liver where DNA damage was dropped more than half below controls, and also in the kidneys. Only the lungs didn't see a significant decrease in DNA damage, which is probably due to the fact the lungs already had extremely low levels of damage even in the control mice compared to all the other tissues (figure 3). What is also cool is that the mice on resveratrol were slimmer and did not gain weight like the control mice did - they stayed slim and did not go above 40 grams, while control mice did (figure 2).

As to the increase of prostaglandin and protein carbonyl in the kidneys, their table shows that urinary creatinine was not changed between the resveratrol and control groups, meaning the kidneys were functioning equally well in both groups of mice. So, the resveratrol group were not suffering any sort of kidney degradation.

It is possible the increase of these factors in the kidneys might have been due to better clearance from other tissues, or increased mitochondrial activity. Still, DNA damage is far more important to guard against than oxidation of lipids and proteins (they usually then lead to DNA damage, except with resveratrol around, these results suggest), as we already have plenty of antioxidants to protect them (vitamin E and C respectively) Also, we've never seen evidence of kidney damage, that I know of, even in mice taking doses far far beyond what these mice were (in fact, resveratrol has been shown to protect from renal necrosis due to lipid peroxidation, here. Perhaps this has to do with its remarkable DNA protection?). Very interesting results though, and I hope they do some follow up studies on resveratrol and kidneys.

On a technical note, the mice were taking about a 10mg/kg dose of resveratrol.

Edited by geddarkstorm, 27 January 2009 - 01:42 AM.

[zorba990]

What's really cool to me about this paper, is how they show resveratrol, especially resveratrol taken over 12 months, massively reduced DNA oxidative damage, especially in the heart and the liver where DNA damage was dropped more than half below controls, and also in the kidneys. Only the lungs didn't see a significant decrease in DNA damage, which is probably due to the fact the lungs already had extremely low levels of damage even in the control mice compared to all the other tissues (figure 3). What is also cool is that the mice on resveratrol were slimmer and did not gain weight like the control mice did - they stayed slim and did not go above 40 grams, while control mice did (figure 2).

As to the increase of prostaglandin and protein carbonyl in the kidneys, their table shows that urinary creatinine was not changed between the resveratrol and control groups, meaning the kidneys were functioning equally well in both groups of mice. So, the resveratrol group were not suffering any sort of kidney degradation.

It is possible the increase of these factors in the kidneys might have been due to better clearance from other tissues, or increased mitochondrial activity. Still, DNA damage is far more important to guard against than oxidation of lipids and proteins (they usually then lead to DNA damage, except with resveratrol around, these results suggest), as we already have plenty of antioxidants to protect them (vitamin E and C respectively) Also, we've never seen evidence of kidney damage, that I know of, even in mice taking doses far far beyond what these mice were (in fact, resveratrol has been shown to protect from renal necrosis due to lipid peroxidation, here. Perhaps this has to do with its remarkable DNA protection?). Very interesting results though, and I hope they do some follow up studies on resveratrol and kidneys.

On a technical note, the mice were taking about a 10mg/kg dose of resveratrol.

I really hate these studies where they add the nutrient to the water.

What if the body wants to flush more toxins and increases urine output? Then
drinking more water to keep up results in a larger dose.

[geddarkstorm]

I really hate these studies where they add the nutrient to the water.

What if the body wants to flush more toxins and increases urine output? Then
drinking more water to keep up results in a larger dose.

True. Their kidneys didn't suffer any from the performance marker of creatinine secretion, nor have they in any other study, so it doesn't worry me. Now, if someone was currently undergoing kidney failure, resveratrol might put a bigger strain on them according to this data, but it is still hard to say conclusively - still, I wouldn't advice such people to take resveratrol until we know more.

Edited by geddarkstorm, 27 January 2009 - 06:17 AM.