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Dysfunction of basal ganglia neurons is a characteristic of glutaric acidemia type I (GA-I), an autosomal recessive inherited neurometabolic disease characterized by deficiency of glutaryl-CoA dehydrogenase (GCDH) and accumulation of glutaric acid (GA). The affected patients present clinical manifestations such as motor dysfunction and memory impairment followed by extensive striatal neurodegeneration. Knowing that there is relevant striatal dysfunction in GA-I, the purpose of the present study was to verify the performance of young rats chronically injected with GA in working and procedural memory test, and whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Rat pups were injected with GA (5 μmol g body weight−1, subcutaneously; twice per day; from the 5th to the 28th day of life) and were supplemented with NAC (150 mg/kg/day; intragastric gavage; for the same period). We found that GA injection caused delay procedural learning; increase of cytokine concentration, oxidative markers, and caspase levels; decrease of antioxidant defenses; and alteration of acetylcholinesterase (AChE) activity. Interestingly, we found an increase in glial cell immunoreactivity and decrease in the immunoreactivity of nuclear factor-erythroid 2-related factor 2 (Nrf2), nicotinic acetylcholine receptor subunit alpha 7 (α7nAChR), and neuronal nuclei (NeuN) in the striatum. Indeed, NAC administration improved the cognitive performance, ROS production, neuroinflammation, and caspase activation induced by GA. NAC did not prevent neuronal death, however protected against alterations induced by GA on Iba-1 and GFAP immunoreactivities and AChE activity. Then, this study suggests possible therapeutic strategies that could help in GA-I treatment and the importance of the striatum in the learning tasks.

The accumulation of advanced oxidation protein products (AOPPs) has been linked to several pathological conditions. Here, we investigated collagen as a potential source for AOPP formation and determined the effects of hypochlorous acid (HOCl)-treated collagen (collagen-AOPPs) on human neutrophil activity. We also assessed whether alpha-tocopherol could counteract these effects. Exposure to HOCl increased the levels of collagen-AOPPs. Collagen-AOPPs also stimulated the production of AOPPs, nitric oxide (NO), superoxide radicals (O2 −), and HOCl by neutrophils. Collagen-AOPPs induced apoptosis and decreased the number of viable cells. Alpha-tocopherol prevented the formation of collagen-AOPPs, strongly inhibited the collagen-AOPP-induced production of O2 − and HOCl, and increased the viability of neutrophils. Our results suggest that collagen is an important protein that interacts with HOCl to form AOPPs, and consequently, collagen-AOPP formation is related to human neutrophil activation and cell death.

Multiple sclerosis (MS) is an autoimmune neurological disorder of unknown etiology. Oxidative stress and alterations in vitamin D levels have been implicated in the pathophysiology of MS. The aim of this study was to investigate δ-aminolevulinate dehydratase (δ-ALA-D) activity as well as the levels of vitamin D, lipid peroxidation levels, carbonyl protein content, DNA damage, superoxide dismutase (SOD) and catalase (CAT) activities, and the vitamin C, vitamin E, and non-protein thiol (NPSH) content in samples from patients with the relapsing-remitting form of MS (RRMS). The study population consisted of 29 RRMS patients and 29 healthy subjects. Twelve milliliters of blood was obtained from each individual and used for biochemical determinations. The results showed that δ-ALA-D and CAT activities were significantly increased, while SOD activity was decreased in the whole blood of RRMS patients compared to the control group (P < 0.05). In addition, we observed a significant increase in lipid peroxidation, carbonyl protein levels in serum and damaged DNA in leucocytes in RRMS patients compared with the control group (P < 0.05). Nonetheless, the levels of vitamin C, vitamin E, NPSH, and vitamin D were significantly decreased in RRMS patients in relation to the healthy individuals (P < 0.05). In conclusion, our results suggested that the increase in δ-ALA-D activity may be related to the inflammatory and immune process in MS in an attempt to maintain the cellular metabolism and reduce oxidative stress. Moreover, the alterations in the oxidant/antioxidant balance and lower vitamin D levels may contribute to the pathophysiology of MS.

Resveratrol is an molecule that provides both anti-inflammatory and antioxidant properties. However, it is unclear whether the basal oxidative state of the cell has any influence on the effects of this compound. In humans, a single nucleotide polymorphism (SNP) is present in the enzyme manganese superoxide dismutase (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA- and VV-genotypes result in higher or lower enzymatic activity, respectively. Furthermore, the VV-genotype has been associated with high levels of inflammatory cytokines. Here, we examined the effects of a range of resveratrol concentrations on the in vitro activation of human peripheral blood mononuclear cells (PBMCs) carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative biomarkers and cytokines (IL-1β, IL-6, TNFα, Igγ and IL-10) were analyzed. In addition, the effects of resveratrol on the expression of the sirt1 gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At 10 µM resveratrol, there was a significant decrease in the production of inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a subtle decrease in these, except for TNFα, which was not affected. In all SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1 levels. Together, these results suggest that the effect of resveratrol on human PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP.

Background Nowadays, Type 2 Diabetes Mellitus (T2D) affects a significant percentage of the world population. Due to the high levels of glucose, it causes several damages to the cells and, consequently, to the organism. Plants, such as guarana (Paullinia cupana), which present bioactive compounds, could help somehow in the treatment of diabetes and other chronic diseases. Studies have shown that guarana extract, rich in compounds like methylxanthines, theobromine and theophylline, presents many beneficial effects to the organism, such as antioxidant capacity, modulation of nitric oxide intracellular levels, as well as anti-obesity and anti-inflammatory capacity.

Guarana powder is an antiobesogenic supplement; however, its effect on inflammatory biomarkers has not yet been determined. Therefore, this study analysed whether guarana supplementation can differentially modulate the levels of proinflammatory cytokines [interleukin 6 (IL-6), tumour necrosis factor-alpha, interleukin 1 beta (IL-1β), interferon-gamma (Ig-γ)] and anti-inflammatory interleukin 10 (IL-10) from in vitro and in vivo protocols. In the pilot in vitro protocol, human peripheral blood mononuclear cells were exposed to guarana, as well as to resveratrol, quercetin and ascorbic acid as positive controls. The effect of guarana on cytokine levels was also evaluated in culture medium supplemented with glucose and insulin. A randomised, placebo-controlled in vivo assay was also performed to evaluate the potential influence of guarana on the blood cytokine levels of 14 healthy volunteers supplemented for 14 days. The effect of guarana was similar to that of resveratrol, a known anti-inflammatory molecule, decreasing IL-1β, IL-10 and Ig-γ levels and increasing IL-10 levels compared to those of the control group. The in vitro insulin supplementation potentiated the effect of guarana on some cytokines. A decreasing effect on the blood inflammatory cytokine levels, along with an increase in IL-10 levels, was also observed in volunteers supplemented with guarana. In conclusion, guarana positively modulates cytokines associated with inflammatory metabolism.