PMC:2944646 / 27675-30471 JSONTXT

{"project":"TEST0","denotations":[{"id":"20877425-71-79-198964","span":{"begin":1003,"end":1007},"obj":"[\"16284628\"]"},{"id":"20877425-234-242-198965","span":{"begin":1778,"end":1782},"obj":"[\"7655763\"]"}],"text":"Summing up\nThe data presented clearly show that piracetam protects mitochondria against different conditions associated with oxidative stress including aging. Piracetam's protecting effects on mitochondrial damage induced in vitro are small, but reproducible and highly significant. This is not surprising, since the conditions used to induce oxidative stress in vitro are not pathophysiological but rather aggressive, in contrast to the small and slowly occurring changes induced by aging, which however were sometimes completely reversed by piracetam treatment. This was also the case for the adaptive elevation of antioxidant enzyme activities. When mild conditions were used in vitro (e.g. partial serum deprivation), a complete protection of mitochondrial function was seen by piracetam treatment in PC12 cells. Moreover, piracetam was highly effective in vivo in pathophysiologically relevant situations of brain dysfunction.\nPiracetam does not possess radical scavenging properties (Keil et al., 2006). Thus, it seems quite likely that piracetam acts directly at the mitochondrial level, presumably by improving mitochondrial membrane properties. This is also supported by our observation that in several experiments protective effects were also seen in the recovery phase, when the oxidative stressor was already removed. Moreover, experiments from our lab also indicate comparable effects of piracetam on isolated mouse brain mitochondria of animals treated with piracetam. The concentrations of piracetam effective in vitro (100–1000 μM) and the doses used in the in vivo experiments (100–500 mg/kg) are quite well within the plasma concentrations seen in patients treated with the standard dose of about 5 g daily, which range between 200 and 2000 μM (Saletu et al., 1995; Wang et al., 2010). Thus, it is quite likely that similar effects are also taking place in the brain of piracetam treated patients. Moreover, a recent pharmacokinetic study in rats indicates plasma concentrations around 500–1000 μmol/l at oral doses of 500 mg/kg BW (Wang et al., 2010).\nWhile the interaction of piracetam with neuronal membranes shows little changes of membrane properties under normal conditions, it significantly enhances reduced membrane fluidity, for example, in the aging or even Alzheimer brain. All the conditions associated with positive effects of piracetam on mitochondrial function in the experiments reviewed above also seem to be associated with decreased membrane fluidity mainly due to enhanced lipids peroxidation. Thus, it seems quite plausible that piracetam improves mitochondrial function by enhancing fluidity of mitochondrial membranes, which seems to be a critical factor regulating mitochondrial function. However, direct proof for this mechanism still needs to be shown."}

{"project":"0_colil","denotations":[{"id":"20877425-16284628-198964","span":{"begin":1003,"end":1007},"obj":"16284628"},{"id":"20877425-7655763-198965","span":{"begin":1778,"end":1782},"obj":"7655763"}],"text":"Summing up\nThe data presented clearly show that piracetam protects mitochondria against different conditions associated with oxidative stress including aging. Piracetam's protecting effects on mitochondrial damage induced in vitro are small, but reproducible and highly significant. This is not surprising, since the conditions used to induce oxidative stress in vitro are not pathophysiological but rather aggressive, in contrast to the small and slowly occurring changes induced by aging, which however were sometimes completely reversed by piracetam treatment. This was also the case for the adaptive elevation of antioxidant enzyme activities. When mild conditions were used in vitro (e.g. partial serum deprivation), a complete protection of mitochondrial function was seen by piracetam treatment in PC12 cells. Moreover, piracetam was highly effective in vivo in pathophysiologically relevant situations of brain dysfunction.\nPiracetam does not possess radical scavenging properties (Keil et al., 2006). Thus, it seems quite likely that piracetam acts directly at the mitochondrial level, presumably by improving mitochondrial membrane properties. This is also supported by our observation that in several experiments protective effects were also seen in the recovery phase, when the oxidative stressor was already removed. Moreover, experiments from our lab also indicate comparable effects of piracetam on isolated mouse brain mitochondria of animals treated with piracetam. The concentrations of piracetam effective in vitro (100–1000 μM) and the doses used in the in vivo experiments (100–500 mg/kg) are quite well within the plasma concentrations seen in patients treated with the standard dose of about 5 g daily, which range between 200 and 2000 μM (Saletu et al., 1995; Wang et al., 2010). Thus, it is quite likely that similar effects are also taking place in the brain of piracetam treated patients. Moreover, a recent pharmacokinetic study in rats indicates plasma concentrations around 500–1000 μmol/l at oral doses of 500 mg/kg BW (Wang et al., 2010).\nWhile the interaction of piracetam with neuronal membranes shows little changes of membrane properties under normal conditions, it significantly enhances reduced membrane fluidity, for example, in the aging or even Alzheimer brain. All the conditions associated with positive effects of piracetam on mitochondrial function in the experiments reviewed above also seem to be associated with decreased membrane fluidity mainly due to enhanced lipids peroxidation. Thus, it seems quite plausible that piracetam improves mitochondrial function by enhancing fluidity of mitochondrial membranes, which seems to be a critical factor regulating mitochondrial function. However, direct proof for this mechanism still needs to be shown."}

{"project":"2_test","denotations":[{"id":"20877425-16284628-38148057","span":{"begin":1003,"end":1007},"obj":"16284628"},{"id":"20877425-7655763-38148058","span":{"begin":1778,"end":1782},"obj":"7655763"}],"text":"Summing up\nThe data presented clearly show that piracetam protects mitochondria against different conditions associated with oxidative stress including aging. Piracetam's protecting effects on mitochondrial damage induced in vitro are small, but reproducible and highly significant. This is not surprising, since the conditions used to induce oxidative stress in vitro are not pathophysiological but rather aggressive, in contrast to the small and slowly occurring changes induced by aging, which however were sometimes completely reversed by piracetam treatment. This was also the case for the adaptive elevation of antioxidant enzyme activities. When mild conditions were used in vitro (e.g. partial serum deprivation), a complete protection of mitochondrial function was seen by piracetam treatment in PC12 cells. Moreover, piracetam was highly effective in vivo in pathophysiologically relevant situations of brain dysfunction.\nPiracetam does not possess radical scavenging properties (Keil et al., 2006). Thus, it seems quite likely that piracetam acts directly at the mitochondrial level, presumably by improving mitochondrial membrane properties. This is also supported by our observation that in several experiments protective effects were also seen in the recovery phase, when the oxidative stressor was already removed. Moreover, experiments from our lab also indicate comparable effects of piracetam on isolated mouse brain mitochondria of animals treated with piracetam. The concentrations of piracetam effective in vitro (100–1000 μM) and the doses used in the in vivo experiments (100–500 mg/kg) are quite well within the plasma concentrations seen in patients treated with the standard dose of about 5 g daily, which range between 200 and 2000 μM (Saletu et al., 1995; Wang et al., 2010). Thus, it is quite likely that similar effects are also taking place in the brain of piracetam treated patients. Moreover, a recent pharmacokinetic study in rats indicates plasma concentrations around 500–1000 μmol/l at oral doses of 500 mg/kg BW (Wang et al., 2010).\nWhile the interaction of piracetam with neuronal membranes shows little changes of membrane properties under normal conditions, it significantly enhances reduced membrane fluidity, for example, in the aging or even Alzheimer brain. All the conditions associated with positive effects of piracetam on mitochondrial function in the experiments reviewed above also seem to be associated with decreased membrane fluidity mainly due to enhanced lipids peroxidation. Thus, it seems quite plausible that piracetam improves mitochondrial function by enhancing fluidity of mitochondrial membranes, which seems to be a critical factor regulating mitochondrial function. However, direct proof for this mechanism still needs to be shown."}