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Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxida


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#1 drmz

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Posted 22 August 2009 - 09:10 AM


Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxidant during day-time and antioxidant at night.
Gadacha W, Ben-Attia M, Bonnefont-Rousselot D, Aouani E, Ghanem-Boughanmi N, Touitou Y.
Laboratoire de Biochimie Médicale et Biologie Moléculaire, INSERM U 13, Faculté de Médecine Pierre et Marie Curie, Paris, France.

We investigated the dosing-time dependency of acute resveratrol administration on lipoperoxidation level found in the heart, liver and kidney of male rats synchronized with a 12-h dark-light cycle. Resveratrol was administered by the i.p. route at the middle of the dark (6 h after dark onset, HADO) or light span (18 HADO) and thiobarbituric acid reactive species (TBARS) measured 4 h later at 10 and 22 HADO, respectively. Basal TBARS levels in the three organs were higher during the night span when compared to day span. Resveratrol effect on tissues TBARS was also dosing-time dependent. When administered during the dark phase, resveratrol decreased TBARS levels whereas at the light span, the polyphenol increased TBARS in the three organs. Resveratrol behaved as an antioxidant during the dark span and as a pro-oxidant during the light span. These data suggested a day/night rhythm in basal lipoperoxidation and in resveratrol antioxidant effect.

#2 maxwatt

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Posted 22 August 2009 - 03:25 PM

I would have liked to see results of administration at the beginning rather than the middle of the sleep/wake cycles. In humans, the Boocock study found higher serum levels with morning administration in humans. Resveratrol also affects CLK genes, and interacts with circadian rhythms.

Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent.
Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-52.
PMID: 17548692

Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers.
Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P.
Mol Nutr Food Res. 2009 May;53 Suppl 1:S7-15.
PMID: 19194969 [PubMed - in process]

Resveratrol regulates circadian clock genes in Rat-1 fibroblast cells.
Oike H, Kobori M.
Biosci Biotechnol Biochem. 2008 Nov;72(11):3038-40. Epub 2008 Nov 7.
PMID: 18997419

Edited by maxwatt, 22 August 2009 - 03:25 PM.


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#3 niner

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Posted 22 August 2009 - 04:50 PM

Resveratrol opposite effects on rat tissue lipoperoxidation: pro-oxidant during day-time and antioxidant at night.
Gadacha W, Ben-Attia M, Bonnefont-Rousselot D, Aouani E, Ghanem-Boughanmi N, Touitou Y.
Laboratoire de Biochimie Médicale et Biologie Moléculaire, INSERM U 13, Faculté de Médecine Pierre et Marie Curie, Paris, France.

We investigated the dosing-time dependency of acute resveratrol administration on lipoperoxidation level found in the heart, liver and kidney of male rats synchronized with a 12-h dark-light cycle. Resveratrol was administered by the i.p. route at the middle of the dark (6 h after dark onset, HADO) or light span (18 HADO) and thiobarbituric acid reactive species (TBARS) measured 4 h later at 10 and 22 HADO, respectively. Basal TBARS levels in the three organs were higher during the night span when compared to day span. Resveratrol effect on tissues TBARS was also dosing-time dependent. When administered during the dark phase, resveratrol decreased TBARS levels whereas at the light span, the polyphenol increased TBARS in the three organs. Resveratrol behaved as an antioxidant during the dark span and as a pro-oxidant during the light span. These data suggested a day/night rhythm in basal lipoperoxidation and in resveratrol antioxidant effect.

Wow. I wish they had put some numbers in the abstract. I'd really like to know the magnitudes of these effects and the doses used. Without that, we don't know if this is something to be concerned about or an interesting curiosity related to the other circadian effects of the compound. It's interesting that TBARS has a circadian pattern even without resveratrol; it's higher at night according to these guys. TBARS encompasses free radical marker compounds like malondialdehyde. The pubmed link is http://pmid.us/19695122 without a link to the text. The ref is:

"Redox report : communications in free radical research" 2009;14(4):154-8. Anyone have access to this obscure journal? Resveratrol is a pretty complicated compound, isn't it?

#4 drmz

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Posted 24 August 2009 - 04:45 PM

mailed the authors for more infomation.

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#5 Michael

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Posted 25 August 2009 - 04:47 PM

All:

I would have liked to see results of administration at the beginning rather than the middle of the sleep/wake cycles. In humans, the Boocock study found higher serum levels with morning administration in humans. Resveratrol also affects CLK genes, and interacts with circadian rhythms.


Actually, it is probably even more complicated than you realize: rats are nocturnal, and are ACTIVE in the middle of the night despite having elevated melatonin (an "antioxidant," whatever that means). And if they buggered with their sleep cycle to reverse that, well, that's another complication.

Perhaps more important: as I documented some time ago on the CR Society list, TBARS is a very unreliable measure of oxidative stress, to the point where I think it can only be read to indicate "something is different here" and not much else; and even further complicating matters, it appears that Calorie restriction initially elevates TBARS levels, even tho' it prevents a subsequent age-related increase therein, making the interpretation of this study's implications for resveratrol as a possible CR mimetic even more fraught.

-Michael

Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent.
Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1246-52.
PMID: 17548692

Resveratrol regulates circadian clock genes in Rat-1 fibroblast cells.
Oike H, Kobori M.
Biosci Biotechnol Biochem. 2008 Nov;72(11):3038-40. Epub 2008 Nov 7.
PMID: 18997419




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