Serotonergic mechanisms associated with experimental models of hypoxia: A systematic review.

PURPOSE: The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5-HT transporter, and 5-HT receptor. METHODS: Literature searches were performed in Embase, Medline (PubMed), Web of Science, and SCOPUS, from April to July 2021, with a total of 1045 published studies found. Using a predefined protocol, as registered on the CAMARADES website, 10 articles were included in this review. The PRISMA statement was used for reporting this systematic review. The internal validity was assessed using the SYRCLE's risk of bias tool. RESULTS: Our main findings show that hypoxia in the first days of postnatal life led to a disturbance in the serotonergic system with reduced in 5-HT fibers, reduced brain levels of 5-HT and 5-HIAA, reduced SERT protein expression, and reduced receptor 5-HT7 . Putative mechanisms involving damage in the serotoninergic system include retrograde cell death resulting from primary damage mainly in forebrain areas, which impairs remote areas including serotonergic raphe nuclei. Other probable mechanisms associated with the serotoninergic network damage may be triggered by excitotoxic lesion and neuroinflammation. CONCLUSION: Hypoxia at the beginning of an animal's life leads to modification of the serotonergic components associated with putative mechanisms that include cell damage and neuroinflammation.

Effect of vitamin A supplementation on iron status in humans: A systematic review and meta-analysis.

Anemia is a worldwide public health problem that can be related to many causes, including vitamin A deficiency. The aim of this study was to assess and estimate the effect of vitamin A supplementation (VAS) on iron status biomarkers and anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed, Scopus and Web of Science, were searched for clinical trials and cohort studies that investigated the effect of vitamin A supplementation alone on iron status and anemia, without time-restriction. The search yielded 23 eligible studies, 21 clinical trials and 2 cohort studies, with children, teenagers, pregnant or lactating women. The meta-analysis of the clinical trials showed that VAS reduces the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated group, independent of the life stage. VAS did not alter the prevalence of iron deficiency among the clinical trials conducted with children and teenagers (RR 0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum ferritin levels was observed in trials conducted with pregnant and lactating women (WMD 6.61 µg/L; 95% CI 6.00 to 7.21 µg/L; p < 0.001). Therefore, vitamin A supplementation alone may reduce the risk of anemia, by improving hemoglobin and ferritin levels in individuals with low serum retinol levels.

Tucum-do-cerrado (Bactris setosa Mart.) may enhance hepatic glucose response by suppressing gluconeogenesis and upregulating Slc2a2 via AMPK pathway, even in a moderate iron supplementation condition.

Dietary phytochemicals may improve glucose metabolism while iron excess seems to be associated to impaired glucose homeostasis and insulin responses. This study investigated the effect of tucum-do-cerrado (Bactris setosa Mart.) consumption on the carbohydrate metabolism and redox response in rats supplemented or not with dietary iron. Male wistar rats were treated with one of the following diets: CT: control diet (AIN- 93G); +Fe: iron-enriched diet; Tuc: control diet +15% tucum-do-cerrado or Tuc + Fe: iron-enriched diet +15% tucum-do-cerrado. Iron supplementation increased muscle lipid and protein oxidation, hepatic glucokinase (GK) and phosphofrutokinase 1 (PFK1) activities and decreased hepatic glucose-6-phosphatase (G6Pase), intestinal Scl2a2 and muscle Slc2a4 and Prkaa2α mRNA levels compared to CT group. Tucum-do-cerrado consumption (Tuc) increased hepatic Slc2a2, Prkaa1α, Prkaa2α and intestinal Slc5a1 mRNA levels, also decreased hepatic G6Pase activity, muscle Slc2a4 and Prkaa2α in relation to CT group. The association of tucum-do-cerrado with iron-enriched diet increased hepatic Prkaa1 and Pck1 compared to the CT and + Fe groups, intestinal Slc2a2 mRNA levels compared to the +Fe group, while decreased hepatic G6Pase activity in relation to the CT, +Fe and Tuc + Fe groups and muscle Slc2a4 and Prkaa2α compared to CT group. These results suggest that tucum-do-cerrado consumption might induce Prkaa1α and Prkaa2α expression, which may inhibit gluconeogenic rate limiting enzyme, G6Pase, and upregulates GLUT2 hepatic glucose uptake. In addition, moderate iron supplementation improves intracellular hepatic glucose response, stimulating the glycolytic rate limiting enzymes GK and PFK1 while inhibiting gluconeogenic enzyme G6Pase.

L-tryptophan administration and increase in cerebral serotonin levels: Systematic review.

The amino acid tryptophan (2-Amino-3-(lH-indol-3-yl)-propanoic acid; Trp) is a precursor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) that performs various brain functions. The administration of Trp is used in experimental studies to manipulate the serotonergic system, however the dose of Trp required to raise brain 5-HT levels is controversial. The aim of this study was to systemically review the effect of the administration of different doses of Trp on cerebral 5-HT levels. Two independent authors conducted a systematic review in the electronic databases. Twenty-five studies were included in the present review. Trp was administered orally, intraperitoneally or subcutaneous in adult animals. The brain 5-HT levels elevated after Trp administration in different intensities, dependent of the brain region evaluated and the time of administration. Further studies are needed to assess the dose-response of Trp administration to brain 5-HT levels.

A systematic review on phenolic compounds in Passiflora plants: Exploring biodiversity for food, nutrition, and popular medicine.

Passiflora plants are strategic in the context of biodiversity for food and nutrition. We applied the procedures of a systematic review protocol to study the state of the art on identification of phenolic compounds from Passiflora plants. An automated literature search was conducted using six databases and a combination of seven keywords. All the analytical, chromatographic, and spectroscopic methods were included. The studies were classified according to their method of identification, phenolic classes, and method of extraction. In total, 8,592 abstracts were found, from which 122 studies were selected for complete reading and 82 were selected for further analysis. Techniques of extraction, evaluated parts of the plant and methods of identification were systematized. Studies with leaves were most conspicuous (54.4%), 34 species of Passiflora were evaluated and orientin, isoorientin, vitexin, isovitexin were commonly found structures. A High Performance Liquid Chromatography-diode array detector was the technique most applied, with which the same structures were identified all through the studies, although other unknown structures were detected, but not elucidated. The use of Nuclear Magnetic Resonance and Mass Spectrometry, which are more sensitive techniques, needs to be intensified, to identify other unconventional compounds detected in Passiflora, to enhance the comprehension of the bioactive compounds in these plants.

Tucum-do-Cerrado (Bactris setosa Mart.) May Promote Anti-Aging Effect by Upregulating SIRT1-Nrf2 Pathway and Attenuating Oxidative Stress and Inflammation.

Aging may be related to oxidative damage accumulation and a low-grade inflammation, both responses are modulated by iron and phytochemicals. This study investigated the effect of tucum-do-cerrado (Bactris setosa Mart.) consumption on the expression of sirtuins (SIRT 1 and 3) and senescence marker protein-30 (SMP30), and on the redox and inflammatory responses, in adult rats supplemented or not with dietary iron. Male Wistar rats were treated for 12 weeks with: control diet (CT); iron enriched-diet (+Fe); control diet + 15% tucum-do-cerrado (Tuc); or iron enriched-diet + 15% tucum-do-cerrado (Tuc + Fe). Iron supplementation (+Fe) increased liver, spleen and intestine iron levels, transferrin saturation, serum iron, serum TNF-α and IL-6 levels, hepatic carbonyl content and and superoxide dismutase (SOD) activity, hepatic Nrf2 protein and Nqo1 mRNA levels and decreased the renal Sirt1 mRNA levels in relation to CT group. Tucum-do-cerrado consumption (Tuc) increased hepatic SOD activity, Nrf2 and SIRT1 mRNA and protein contents, and Nqo1 mRNA levels, while it decreased the renal SOD activity compared with the CT diet. The consumption of tucum-do-cerrado associated with the iron-enriched diet (Tuc + Fe) increased the iron levels in tissues and serum transferrin saturation, compared to the CT diet, while promoting a decrease in hepatic carbonyl and renal malondialdehyde levels, marginally reducing serum IL-6 levels, and increasing hepatic SIRT1 protein content, renal Sirt1 and hepatic Nrf2 mRNA levels, compared to the +Fe group. None of the treatments altered Smp30 mRNA levels. The results suggest that tucum-do-cerrado consumption might promote an anti-aging effect by increasing SIRT1 expression, which may enhance Nrf2 mRNA and protein levels and its downstream pathway, which in turn decrease oxidative damage to proteins and the levels of inflammatory cytokines (IL-6 and TNF-α), induced by iron excess.