Autism spectrum disorders (ASDs), which include the prototypic autistic disorder (AD), Asperger’s syndrome (AS) and pervasive developmental disorders not otherwise specified (PDD-NOS), are complex neurodevelopmental conditions of unknown aetiology. The current study investigated the metabolites in the methionine cycle, the transsulphuration pathway, folate, vitamin B12 and the C677T polymorphism of the MTHFR gene in three groups of children diagnosed with AD (n= 15), AS (n= 5) and PDD-NOS (n= 19) and their age- and sex-matched controls (n= 25). No metabolic disturbances were seen in the AS patients, while in the AD and PDD-NOS groups, lower plasma levels of methionine (P= 0.01 and P= 0.03, respectively) and α-aminobutyrate were observed (P= 0.01 and P= 0.001, respectively). Only in the AD group, plasma cysteine (P= 0.02) and total blood glutathione (P= 0.02) were found to be reduced. Although there was a trend towards lower levels of serine, glycine, N, N-dimethylglycine in AD patients, the plasma levels of these metabolites as well as the levels of homocysteine and cystathionine were not statistically different in any of the ASDs groups. The serum levels of vitamin B12 and folate were in the normal range. The results of the MTHFR gene analysis showed a normal distribution of the C677T polymorphism in children with ASDs, but the frequency of the 677T allele was slightly more prevalent in AD patients. Our study indicates a possible role for the alterations in one carbon metabolism in the pathophysiology of ASDs and provides, for the first time, preliminary evidence for metabolic and genetic differences between clinical subtypes of ASDs.

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Zinc (Zn) and copper (Cu) are important trace elements for cognitive development and normal neurological functioning. Autism spectrum disorder (ASD) is a common neurological disorder, which has previously been associated with the levels of some trace elements in the blood. However, clinical data regarding the potential implication of Zn and Cu in patients with ASD are still insufficient. Therefore, the aim of the present study was to investigate the whole blood levels of Zn and Cu in a cohort of 28 children with ASD and 28 age- and gender-matched healthy controls. Whole blood Zn and Cu levels were assessed using inductively-coupled plasma-sector field mass spectrometry. Both in the control and in the ASD group, the values of whole blood Cu and Zn were characterized by a Gaussian distribution. The results indicate that the ASD children were characterized by ~10 % (p = 0.005) and ~12 % (p = 0.015) lower levels of whole blood Zn and Zn/Cu ratio, respectively, in comparison to controls. No significant difference in whole blood Cu was observed. However, Cu/Zn ratio was ~15 % (p = 0.008) higher in ASD children than that in the control ones. The results of the present study may be indicative of Zn deficiency in ASD children. Taking into account Zn-mediated up-regulation of metallothionein (MT) gene expression, these findings suggest a possible alteration in the functioning of the neuroprotective MT system. However, further investigations are required to test this hypothesis.

All paraoxonase-1 activities were lower in diabetic children and adolescents, but only the decrease in the lactonase activity was statistically significant. Although lipid profile and glycaemic control were altered in diabetics, no differences were observed between groups regarding oxidized LDL level.

Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today's alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma oxidative stress induced by fructose intake, in rats. Sprague-Dawley rats (48 animals) were randomized into two series (n = 24): rats fed with standard chow or with standard chow supplemented with 60% fructose. In each of the two series, for 2 weeks/month over 12 weeks, a group of rats (n = 12) was intraperitoneally injected with NaCl 0.9%, and a second group (n = 12) received AL 50 mg/kg/day. Body weight, glycemia, and systolic blood pressure were monitored throughout the study. After 12 weeks, IR, plasma lipoproteins, uric acid, transaminase activities, and oxidative stress markers were assessed. The high fructose-enriched diet induced cardiometabolic disorders (hypertension, hyperglycemia, IR and dyslipidemia), an increase in uric acid concentration, transaminase activities and C-reactive protein level. This diet also enhanced plasma products of lipid and protein oxidation, homocysteine level, and decreased GSH/GSSG ratio. In this field, there is evidence to indicate that oxidative stress plays an important role in the etiology of diabetic complications. AL discontinuous treatment prevents the metabolic disorders induced by fructose intake, reduced plasma lipid and protein oxidation-products, and restored the GHS/GSSG ratio. Our study proves a promising potential of the chronic-discontinuous treatment of AL and highlights the pleiotropic effects of this antioxidant substance in metabolic disorders such as diabetes.

The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.

The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of Sambucus nigra L. elderflower (SN) to inhibit lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL−1), epicatechin (9.0 ± 1.1 µg mL−1), and ferulic (1.5 ± 0.3 µg mL−1) and caffeic acid (3.6 ± 0.1 µg mL−1). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg−1 bw day−1 GM), GM+SN group (100 mg kg−1 bw day−1 GM and 1 mL SN extract day−1), and SN group (1 mL SN extract day−1). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity—superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)—were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group (p < 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group (p = 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group (p > 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.

There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT). We also investigated the angiogenic and fibrotic pathways involved in the mechanism of action of DIAVIT. Diabetic db/db mice developed hyperglycaemia, albuminuria, and an increased glomerular water permeability; the latter two were prevented by DIAVIT. db/db mice developed fibrotic glomeruli, endothelial insult, and glomerular ultra-structural changes, which were not present in DIAVIT-treated mice. Vascular endothelial growth factor A (VEGF-A) splicing was altered in the db/db kidney cortex, increasing the pro-angiogenic VEGF-A165 relative to the anti-angiogenic VEGF-A165b. This was partially prevented with DIAVIT treatment. Delphinidin, an anthocyanin abundant in DIAVIT, increased the VEGF-A165b expression relative to total VEGF-A165 in cultured podocytes through phosphorylation of the splice factor SRSF6. DIAVIT, in particular delphinidin, alters VEGF-A splicing in type II DN, rescuing the DN phenotype. This study highlights the therapeutic potential of natural drugs in DN through the manipulation of gene splicing and expression.