Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules produced naturally by the body and by external factors. When these species are generated in excessive amounts, they can lead to oxidative stress, which in turn can cause cellular and tissue damage. This damage is known to contribute to the aging process and is associated with age-related conditions, including cardiovascular and neurodegenerative diseases. In recent years, there has been an increased interest in the development of compounds with antioxidant potential to assist in the treatment of disorders related to oxidative stress. In this way, compounds containing sulfur (S) and/or selenium (Se) have been considered promising due to the relevant role of these elements in the biosynthesis of antioxidant enzymes and essential proteins with physiological functions. In this context, studies involving heterocyclic nuclei have significantly increased, notably highlighting the indolizine nucleus, given that compounds containing this nucleus have been demonstrating considerable pharmacological properties. Thus, the objective of this research was to evaluate the in vitro antioxidant activity of eight S- and Se-derivatives containing indolizine nucleus and different substituents. The in vitro assays 1,1-diphenyl-2-picryl-hydrazil (DPPH) scavenger activity, ferric ion (Fe3+) reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and protein carbonylation (PC) were used to access the antioxidant profile of the compounds. Our findings demonstrated that all the compounds showed FRAP activity and reduced the levels of TBARS and PC in mouse brains homogenates. Some compounds were also capable of acting as DPPH scavengers. In conclusion, the present study demonstrated that eight novel organochalcogen compounds exhibit antioxidant activity.

Bioactivity of selenium-containing pyridinium salts: Prospecting future pharmaceutical constituents to treat liver diseases involving oxidative stress.

Redox imbalance leads to oxidative stress that causes irreversible cellular damage. The incorporation of the antioxidant element selenium (Se) in the structure of pyridinium salts has been used as a strategy in chemical synthesis and can be useful in drug development. We investigated the antioxidant activity of Se-containing pyridinium salts (named Compounds 3A, 3B, and 3C) through in vitro tests. We focused our study on liver protein carbonylation, liver lipoperoxidation, free radical scavenging activity (1,1-diphenyl-2-picryl-hydrazil [DPPH]; 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid [ABTS]), and enzyme-mimetic activity assays (glutathione S-transferase [GST]-like; superoxide dismutase [SOD]-like). In addition, 2-(4-chlorophenyl)-2-oxoethyl)-2-((phenylselanyl)methyl)pyridin-1-ium bromide (3C) was selected to evaluate the acute oral toxicity in mice due to the best antioxidant profile. The three compounds were effective in reducing the levels of protein carbonylation and lipoperoxidation in the liver in a µM concentration range. All compounds demonstrated scavenger activity of DPPH and ABTS radicals, and GST-like action. No significant effects were detected in the SOD-like assay. Experimental data also showed that the acute oral treatment of mice with Compound 3C (50 and 300 mg/kg) did not cause mortality or change markers of liver and kidney functions. In summary, our findings reveal the antioxidant potential of Se-containing pyridinium salts in liver tissue, which could be related to their radical scavenging ability and mimetic action on the GST enzyme. They also demonstrate a low toxicity potential for Compound 3C. Together, the promising results open space for future studies on the therapeutic application of these molecules.

Critical assessment of the endocrine potential of Linalool and Linalyl acetate: proactive testing strategy assessing estrogenic and androgenic activity of Lavender oil main components.

The acyclic linear monoterpenes Linalool (Lin) and Linalyl acetate (LinAc) occur in nature as major constituents of various essential oils such as lavender oils. A potential endocrine activity of these compounds was discussed in literature including premature thelarche and prepubertal gynecomastia due to lavender product use. This study aims to follow-up on these critical findings reported by testing Lin and LinAc in several studies in line with current guidance and regulatory framework. No relevant anti-/ER and AR-mediated activity was observed in recombinant yeast cell-based screening tests and guideline reporter gene in vitro assays in mammalian cells. Findings in the screening test suggested an anti-androgenic activity, which could not be confirmed in the respective mammalian cell guideline assay. Mechanistic guideline in vivo studies (Uterotrophic and Hershberger assays) with Lin did not show significant dose related changes in estrogen or androgen sensitive organ weights and a guideline reproductive toxicity screening study did not reveal evident effects on sex steroid hormone sensitive organ weights, associated histopathological findings and altered sperm parameters. Estrous cycling and mating/fertility indices were not affected and no evident Lin-related steroid hormone dependent effects were found in the offspring. Overall, the initial concerns from literature were not confirmed. Findings in the yeast screening test were aberrant from follow-up guideline in vitro and in vivo studies, which underlines the need to apply careful interpretation of single in vitro test results to support a respective line of evidence and to establish a biologically plausible link to an adverse outcome.

Recent Advances in the Synthesis and Antioxidant Activity of Low Molecular Mass Organoselenium Molecules.

Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice.

RATIONALE: Depression is a mental disorder that affects approximately 280 million people worldwide. In the search for new treatments for mood disorders, compounds containing selenium and indolizine derivatives show promising results. OBJECTIVES AND METHODS: To evaluate the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine (MeSeI) (0.5-50 mg/kg, intragastric-i.g.) on the tail suspension test (TST) and the forced swim test (FST) in adult male Swiss mice and to elucidate the role of the serotonergic system in this effect through pharmacological and in silico approaches, as well to evaluate acute oral toxicity at a high dose (300 mg/kg). RESULTS: MeSeI administered 30 min before the FST and the TST reduced immobility time at doses from 1 mg/kg and at 50 mg/kg and increased the latency time for the first episode of immobility, demonstrating an antidepressant-like effect. In the open field test (OFT), MeSeI did not change the locomotor activity. The antidepressant-like effect of MeSeI (50 mg/kg, i.g.) was prevented by the pre-treatment with p-chlorophenylalanine (p-CPA), a selective tryptophan hydroxylase inhibitor (100 mg/kg, intraperitoneally-i.p. for 4 days), with ketanserin, a 5-HT2A/2C receptor antagonist (1 mg/kg, i.p.), and with GR113808, a 5-HT4 receptor antagonist (0.1 mg/kg, i.p.), but not with WAY100635, a selective 5-HT1A receptor antagonist (0.1 mg/kg, subcutaneous-s.c.) and ondansetron, a 5-HT3 receptor antagonist (1 mg/kg, i.p.). MeSeI showed a binding affinity with 5-HT2A, 5 -HT2C, and 5-HT4 receptors by molecular docking. MeSeI (300 mg/kg, i.g.) demonstrated low potential to cause acute toxicity in adult female Swiss mice. CONCLUSION: In summary, MeSeI exhibits an antidepressant-like effect mediated by the serotonergic system and could be considered for the development of new treatment strategies for depression.

Presence of a companion in the delivery room and breastfeeding in the first hour of life: is there an association? / Presença de acompanhante na sala de parto e aleitamento materno na primeira hora de vida: há associação?

Abstract Objectives: to identify variables associated with the presence of a companion in the delivery room and its association with breastfeeding (BF) in the first hour of life. Methods: cross-sectional analysis of data from a cohort study (n=344). To investigate the factors associated with the presence of a companion during childbirth and breastfeeding in the first hour; we performed Poisson regression analyses, considering p<0.05 as the level of statistical significance. Results: 93.9% of the pregnant women had a companion in the delivery room, and no association was found between socioeconomic, obstetric and neonatal characteristics of the mother-child binomial and the presence of a companion. In a univariate analysis, the absence of a companion reduced the frequency of breastfeeding in the first hour (PR=0.64; CI95%=0.42-0.96), a result that was not confirmed in the adjusted analyses (PR=0.79; CI95%=0.54-1.15). Secondly, it was identified that the five minutes Apgar score was associated with first hour breastfeeding (PR=1.27; CI95%=1.14-1.40) regardless of the other factors. Conclusions: most women in the cohort had a companion in the delivery room, with no differences according to socioeconomic, obstetric and neonatal variables. The frequency of first hour breastfeeding was high; however, it was lower in the absence of a companion but this association was not independent of other factors.

Resumo Objetivos: identificar variáveis associadas à presença de acompanhante na sala de parto e sua associação com o aleitamento materno (AM) na primeira hora de vida. Métodos: análise transversal de dados provenientes de um estudo de coorte (n=344). Para investigação dos fatores associados entre a presença de companhia durante o parto e o AM na primeira hora foram realizadas análises de regressão de Poisson, considerando p<0,05 como nível de significância estatística. Resultados: 93,9% das parturientes tiveram acompanhante na sala de parto, não sendo encontrada associação entre características socioeconômicas, obstétricas e neonatais do binômio mãe-filho e esta presença. Em análise univariada, a ausência de acompanhante reduziu a frequência de AM na primeira hora (RP=0,64; IC95%=0,42-0,96), resultado que não se confirmou nas análises ajustadas (RP=0,79; IC95%=0,54-1,15). Secundariamente, identificou-se que o Apgar no quinto minuto associou-se com AM na primeira hora (RP=1,27; IC95%=1,14-1,40) independentemente dos demais fatores. Conclusões: a maioria das mulheres da coorte contou com acompanhante na sala de parto, sem diferenças segundo variáveis socioeconômicas, obstétricas e neonatais. A frequência de AM na primeira hora também foi alta e menor na ausência de acompanhante, contudo, essa associação não se mostrou independente de outros fatores.

90-Day Oral Toxicity Assessment of Tropaeolum majus L. in Rodents and Lagomorphs.

Tropaeolum majus L., popularly known as nasturtium, is a species widely used in the form of infusions and salads. In the last years, the antihypertensive, diuretic, and calcium and potassium sparing activities of T. majus preparations were shown. Moreover, no preclinical 90-day oral toxicity studies were conducted. Thus, this study evaluated the toxicity of the hydroethanolic extract obtained from T. majus (HETM) leaves in female and male mice, rats, and rabbits. Swiss mice and Wistar rats were treated with HETM (75, 375, and 750 mg/kg). The doses of rabbits (30, 150, and 300 mg/kg) were calculated by allometric extrapolation. The control groups received vehicle. The animals were orally treated, daily, for 90 days. At the end, the animals were anesthetized, and body weight gain, relative weight of liver, kidney, and spleen, and histopathological changes were evaluated. Serum hematological and biochemical parameters were also analyzed. No alterations were found in body and organ weights or in histopathological and biochemical evaluation. Hematological analyses revealed small changes in lymphocytes and neutrophil counts in rats after administration of 750 mg/kg of HETM. These results showed that 90-day use of T. majus is safe in rodents and lagomorphs.

Effects of Angiotensin-Converting Enzyme Inhibitor Derived from Tropaeolum majus L. in Rat Preimplantation Embryos: Evidence for the Dehydroepiandrosterone and Estradiol Role.

Although several studies have shown the inhibitory effects of Tropaeolum majus extracts (HETM) on angiotensin-converting enzyme (ACE) activity, no studies have been carried out during the beginning of pregnancy, when humoral and hormonal imbalance may affect zygote and early embryo transport. This study investigates whether HETM can affect embryonic development when administered during the one-cell-blastocyst period. Pregnant Wistar rats received orally the HETM (3, 30, and 300 mg/kg/day) from the 1st to the 7th gestational day. Rats were killed on the 8th day of pregnancy and the following parameters were evaluated: clinical symptoms of toxicity (including organ weights), number of corpora lutea, implants per group, preimplantation losses ratio, and the serum levels of dehydroepiandrosterone (DHEA), estradiol, and progesterone. No clinical symptoms of maternal toxicity were evidenced. On the 8th day of pregnancy, the levels of DHEA and estradiol were increased and significant preimplantation losses were observed at all doses used. The present study reveals that the HETM can raise levels of DHEA and estradiol and induce difficulty in the embryo implantation in the early stages of pregnancy. The data contributes significantly to the safety aspects of using this natural product when trying to get pregnant or during pregnancy.

Evaluation of subchronic toxicity of the hydroethanolic extract of Tropaeolum majus in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of medicinal plants for the treatment of diseases usually comes from the belief that they present low toxicity due their natural origin. However, it is necessary a toxicological and pharmacological evaluation for these plants. Tropaeolum majus is a medicinal plant used in popular medicine to treat several diseases, including cardiovascular disorders, urinary tract infections and asthma. Even though several studies proved its therapeutic effects, there are few toxicological studies with this species. AIM OF THE STUDY: The present study was carried out to evaluate the subchronic toxicity of the hydroethanolic extract obtained from leaves of T. majus (HETM) in Wistar rats. MATERIAL AND METHODS: Male and female Wistar rats received three doses of HETM (75, 375 and 750 mg/kg) for 28 days. After the treatments biochemical, hematological and histopathological parameters were analyzed. RESULTS: No significant alterations in the animal's body weight gain, relative organs weight, serum biochemical analysis, hematological or histopathological analyses of liver, kidneys and spleen were observed. CONCLUSIONS: These results demonstrate the absence of subchronic toxicity due to oral treatment with HETM for 28 days in Wistar rats. However, other toxicological studies are necessary to evaluate the total safety of this plant.

Screening for in vivo (anti)estrogenic and (anti)androgenic activities of Tropaeolum majus L. and its effect on uterine contractility.

ETHNOPHARMACOLOGICAL RELEVANCE: Tropaeolum majus L. (Tropaeolaceae) is a medicinal herb popularly used in Brazil for treatment of inflammatory and cardiovascular diseases. Despite some published data on its efficacy, there are still few toxicological data describing the safety of this plant. The aim of this study was to evaluate the (anti)estrogenic and (anti)androgenic activity of the hydroethanolic extract obtained from Tropaeolum majus L. (HETM), as well as its possible effects on uterine contractility. MATERIALS AND METHODS: Three experimental protocols were performed, (a) uterotrophic assay, (b) Hershberger assay and (c) an ex vivo test to investigate the effects of maternal administration of HETM on uterine contractility at the end of pregnancy. In all protocols three doses of the HETM were administered to Wistar rats: 3, 30 and 300mg/kg. RESULTS: In vivo tests for detection of (anti)androgenic and (anti)estrogenic activities did not show any significant alterations. Similarly, no alterations were observed on uterine contractility induced by oxytocin and arachidonic acid. CONCLUSIONS: HETM was unable to produce (anti)estrogenic or (anti)androgenic activities in the short-term in vivo screening assays performed. In addition, there was no evidence that HETM can affect uterine contractility following gestational exposure of rats.