And why isn't its marker MDA a good indicator? Yes, it increased glutathione A LITTLE, which makes the situation a bit better, but total antioxidative capacity decreased.
The measure of antioxidant capacity (AC) considers the cumulative action of all the antioxidants present in plasma and body fluids, thus providing an integrated parameter rather than the simple sum of measurable antioxidants. The capacity of known and unknown antioxidants and their synergistic interaction is therefore assessed, thus giving an insight into the delicate balance in vivo between oxidants and antioxidants. Measuring plasma AC may help in the evaluation of physiological, environmental, and nutritional factors of the redox status in humans. Determining plasma AC may help to identify conditions affecting oxidative status in vivo (e.g., exposure to reactive oxygen species and antioxidant supplementation).
http://www.ncbi.nlm....pubmed/11121717
I decided to look at the full study because the abstract isn't completely clear.
MDA increases with piracetam over ethidium control. High dosage piracetam increased MDA the most out of all the groups.
Malondialdehyde is generated from reactive oxygen species (ROS), and as such is assayed in vivo as a bio-marker of oxidative stress.[3]
https://docs.google....it?usp=drivesdk
TOTAL ANTIOXIDANT CAPACITY decreases with piracetam in both dosages (statistically significant), but not really vinpocetine (never had an issue with vinpocetine). Strangely, TAC went up a little in the higher dosage, but was still significantly lower. My guess is at a certain level of OS, GSH/other endogenous antioxidants production ramped up and combated the OS, but reduced glutathione glutathione isn't an unlimited resource. But still, piracetam likely contribute to OS burden by increasing MDA and possibly other oxidants.
https://docs.google....it?usp=drivesdk
Glutathione increases with the higher dosages of piracetam. But, again, chronic usage doesn't appear to be wise given that glutathione isn't an unlimited resource. Combine sleep deprivation, toxins, etc..and you get too much of an OS burden...
https://docs.google....it?usp=drivesdk
"In case of piracetam, the
highest dose of the drug increased lipid peroxidation in
brain, whilst eliciting increased brain GSH. An intriguing
explanation for these observations is that at their high
concentration, these drugs exhibit pro-oxidant properties
and increase free radical production or act as a free radical
and in this latter case, it is possible that either piratcetam or
vinpocetine react with other free radicals or antioxidant
systems other than glutathione, which is spared in this
condition."
I think the author sums up the findings well in their discussion.
"In summary, findings in the present study indicates that
demyelination due to the local injection of ethidium bromide
into the rat brain is associated with increased oxidative
stress. The study suggests an antioxidant effect for the
nootropic drugs vinpocetine and piracetam at low doses. In
contrast, the higher doses were associated with an increase
in oxidative stress, though both drugs offered significant
protection against GSH depletion induced by ethidium
bromide. The clinical significance of these findings needs
to be determined."
If I only saw these studies, I would be skeptical. But piracetam's common side effects of brain fog suggest that oxidative stress in the hypothalamus is actually happening in people. The longer people take it the more likely they will experience brain fog, especially when combined with other stressor.
Interestingly, it could be from increased dopamine production:
"Piracetam has been reported to increase dopamine in
cortics and striatium [56–58] which might increase free
radical production. Dopamine is subject to auto-oxidation
to semiquinone and quinones generating free radicals such
as superoxide anion, peroxynitrite, hydroxyl radical and
nitrate radical. Semiquinones and quinines themselves can
form conjugates with thiol compounds such as GSH and
L-cysteine, and generate other radicals that are also toxic
[59]. It is therefore possible that at high doses, both vinpocetine
and piracetam might increase free radical production
through their effect on dopamine level in brain."
Okay now to address these points. I'ts too difficult posting using an iphone
Again the study you referenced is entitled: "Oxidative Stress in a Model of Toxic Demyelination in Rat Brain" This is not
analogous to oxidative stress in healthy rat brains. Your theory is founded upon conjecture and quote divorced from context.
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey
matter. Histopathologically, MS is characterized by focal demyelinating lesions throughout the white
matter, which frequently coincide with cortical demyelination and which may be preceded by
apoptotic destruction of oligodendrocytes [74,75]. Additionally, axonal damage is a key feature of MS
pathogenesis that best correlates with permanent neurological deficits in patients. In general, axonal
damage is observed in early as well as chronically demyelinating lesions and, in acute stages, is
associated with the number of infiltrating immune cells. Inflammatory processes with infiltrating
leukocytes play a crucial role in the pathology of the MS lesion mediated by the production of
inflammatory mediators which also involve reactive oxygen species. Yet, also non-inflammatory Int. J. Mol. Sci. 2012, 13 11790
mechanisms such as mitochondrial dysfunction may contribute to neurodegeneration in MS [76].
Excessive release of free radicals may play an important role in MS pathogenesis and promote
transendothelial leukocyte migration as well as contribute to oligodendrocyte damage and as axonal
degeneration [77–80]. Thus, oxidative stress stemming from different cell types and targeting several
cellular components of the CNS to a variable extent is involved in this detrimental concert (Figure 2).
Figure 2. Mechanisms of oxidative injury and cytoprotection in a demyelinating Central
Nervous System (CNS) lesion. Free radicals comprise nitric oxide (NO) and reactive
oxygen as well as nitrogen species (Reactive Oxygen Species (ROS) or Reactive Nitrogen
Species (RNS), respectively) which are mainly produced by macrophages, microglia and
astrocytes. ROS and RNS lead to damage of neurons, axons, myelin and oliogdendrocytes
(indicated by arrows). This process also may involve mitochondrial damage. Black squares
indicate mitochondria which accumulate in injured axons. The cytoptrotective transcription
factor Nrf2 is present in neurons, oligodendrocytes and astrocytes as part of the cellular
anti-oxidative response. Abbreviations: OL, oligodendrocyte; MP, myeloperoxidase.
Does high antioxidant capacity indicate low oxidative stress?
http://cbn.eldoc.ub....lCostantini.pdf
Metabolic activity is a primary source of free radicals,
which are unavoidable by-products of ATP synthesis. Free
radicals, as well as non-free radical pro-oxidants, are prone to
react with any molecules around, causing oxidative damage.
Organisms have evolved multiple defence lines to prevent
oxidative damage, ranging from antioxidant enzymes to low
molecular weight antioxidants, and also specific cellular
components that repair oxidatively damaged molecules. A
disturbance in the balance between pro-oxidants and antioxidants
in favour of the former, leading to oxidative damage,
gives rise to an increase in oxidative stress (Sies 1991; Halliwell
& Gutteridge 2007). Here we define oxidative stress as the rate
at which oxidative damage is generated. Implicit in this
definition is that oxidative stress is a continuous variable that
is unlikely to ever be exactly zero since pro-oxidants are
continually produced and some oxidative damage is always
generated. Persistent oxidative stress may give rise to pathological
conditions and is increasingly implicated as a contributing
factor to several human pathologies (over 150 disorders),
cellular senescence, and aging (Beckman & Ames 1998;
Hulbert
et al
. 2007; Furness & Speakman 2008). Recent
studies show that levels of pro-oxidants and antioxidants may
also have relevant ecological and evolutionary roles and may
help understand functional interactions among life-history
traits (von Schantz
et al
. 1999; Costantini 2008; Monaghan
et al.
2009).
Several methods have been applied to measure antioxidant
capacity of a tissue or single classes of antioxidants (Prior &
Caro 1999; Yeum
et al
. 2004), usually with the aim to quantify
oxidative stress. However, we would like to emphasise in this
note that comparing antioxidant capacity by itself may not
be sufficient to make inferences about differences in levels of
oxidative stress. Although recognized by many, this point has
also been overlooked, in that conclusions on variation in oxidative
stress have often been based on variation in antioxidant levels
alone. Moreover, most commonly, antioxidant enzymes are
measured as indicative of antioxidant capacity without consideration
of the multiple array of non-enzymatic antioxidants
(e.g. thiols, vitamins C and E), which may be very important
to neutralize ROS. As a consequence, both the potential of
antioxidant machinery and the effects of a stressor are underestimated.
An evaluation of the implicit assumption that
information on antioxidant capacity alone allows inferences
on oxidative stress therefore seems useful at this time, given the
growing interest in oxidative stress in evolutionary ecology.
Piracetam failed show radical savaging effect in vitro at human therapeutic doses
In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine.
Comparative evaluation of scavenger properties of exifone, piracetam and vinburnine.
LongeCity
?
