No abstract

There is a great interest in the relationship between Mild Cognitive Impairment (MCI) and the progression to Alzheimer's disease (AD). Several studies show the importance of oxidative stress in the pathogenesis of AD. The purpose of this study was the link between oxidative damage, MCI and AD. It analysed protein carbonyls and erythrocyte glutathione system plasma levels of 34 subjects with MCI, 45 subjects with AD and 28 age-matched control subjects. The results showed an increase in protein modification, a decrease in GSH levels and GSH/GSSG ratio in AD and MCI patients compared to age-matched control subjects (p<0.05). The present study shows that some peripheral markers of oxidative stress appear in MCI with a similar pattern to that observed in AD, which suggests that oxidative stress might represent a signal of the AD pathology. AD and MCI are biochemically equivalent. MCI does not necessarily need to progress to AD on a biochemical level.

No abstract

No abstract

The anti-inflammatory action of most terpenes has been explained in terms of the inhibition of nuclear factor B (NF-B) activity. Ent-kaurene diterpenes are intermediates of the synthesis of gibberellins and inhibit the expression of NO synthase-2 and the release of tumor necrosis factor-␣ in J774 macrophages challenged with lipopolysaccharide. These diterpenes inhibit NF-B and IB kinase (IKK) activation in vivo but failed to affect in vitro the function of NF-B, the phosphorylation and targeting of IB␣, and the activity of IKK-2. Transient expression of NF-B-inducing kinase (NIK) activated the IKK complex and NF-B, a process that was inhibited by kaurenes, indicating that the inhibition of NIK was one of the targets of these diterpenes. These results show that kaurenes impair the inflammatory signaling by inhibiting NIK, a member of the MAPK kinase superfamily that interacts with tumor necrosis factor receptor-associated factors, and mediate the activation of NF-B by these receptors. Moreover, kaurenes delayed the phosphorylation of p38, ERK1, and ERK2 MAPKs, but not that of JNK, in response to lipopolysaccharide treatment of J774 cells. The absence of a coordinate activation of MAPK and IKK might contribute to a deficient activation of NF-B that is involved in the anti-inflammatory activity of these molecules.Activation of the transcription factor NF-B 1 has been shown to be a key component of innate immunity (1), promoting the expression by macrophages of a set of genes involved in host defense, such as pro-inflammatory cytokines (2, 3), NOS-2, cyclooxygenase 2, cell adhesion molecules, and various matrix metalloproteinases (4 -6). NF-B is present constitutively in the cytosol of the cells, where it is retained through the interaction with inhibitory IB proteins that mask the nuclear localization domain of the complex (2). NF-B-dependent gene transcription requires the phosphorylation of IB␣ by IKK2, which releases this inhibitory component from the dimer of Rel proteins (mainly p50, p65, and c-Rel), and is followed by degradation of the phospho-IB by the proteasome (3, 7).Biochemical, pharmacological, and genetic data indicate that the control of NF-B activation constitutes a relevant target for the treatment of inflammatory diseases (2). For this reason, the research on molecules endowed with the capacity to inhibit the consecutive steps leading to NF-B activation has been a subject of current interest (2, 3). In this regard, among the natural products assayed, various terpenoids have been described as potent inhibitors of NF-B activation in response to proinflammatory stimulation. Andalusol, a labdane diterpene from Sideritis exerted anti-inflammatory effects in vivo and in vitro by inhibiting NF-B activation (8, 9). Triterpenes also inhibited NOS-2 expression in RAW 264.7 cells (IC 50 , 0.2-0.3 M) and impaired NF-B activity (10). In the case of sesquiterpenes, it has been described that some of these compounds induce HSP72, which in turn prevents NF-B activation and NOS-2 expression (11, 12).More recently,...

No abstract

The attempt to retard senescence by environmental manipulation includes the use of nutrients or drugs that decrease the oxidative damage to tissues associated with aging. The effects of esculetin treatment (25 mg/kg, orally for 30 days), a phenolic antioxidant compound, on the glutathione system and lipid peroxidation were examined in liver supernatants from male C57BL/6J mice. The effects of esculetin were compared to treatment with 3,5-di-terc-butyl-4-hydroxytoluene (BHT), a well-known synthetic phenolic antioxidant. Reduced glutathione (GSH) concentration in liver supernatants was only increased significantly in esculetin-treated mice compared to control animals, whereas the concentration of oxidized glutathione (GSSG) was significantly decreased by BHT treatment compared to the control group. The GSSG/GSH ratio was significantly lower in esculetin and BHT groups than in the control group. The decrease in this ratio was greater in BHT-treated mice than in esculetin-treated mice. Increases in glutathione reductase (GR) activity were observed with both treatments, although BHT resulted in a superior induction of this activity compared to esculetin. The extent of decline in the GSSG/GSH ratio was correlated with the increase in GR activity. The formation of thiobarbituric acid-reactive substances (TBARs), an index of stress, was lower following treatment with esculetin and BHT compared to control mice (although not significant). This index was very similar for both treatments. Based on the level of TBARs obtained in this study, the accumulation of lipid peroxides declines when the GSH levels are enhanced or GSSG levels are decreased. Finally, we found similar antioxidant effects in vivo with esculetin and BHT treatments and a decrease in the oxidative damage evaluated. The enhancement of glutathione status following esculetin treatment could be a possible defense strategy for the organism under ‘stress conditions’ and may be related to the delay of age-dependent degenerative disorders.

No abstract