Prevalence and predictors of self-medication to prevent or treat COVID-19 among undergraduate students in Southern Brazil.

Self-medication (SM) is the practice of consuming medicines without a prescription. Despite being a potentially dangerous action, SM is practiced globally and has been highlighted during the COVID-19 pandemic. The aim of this study was to evaluate SM for the prevention or treatment of COVID-19 and the factors associated with this practice among undergraduate students in Southern Brazil. A cross-sectional study was conducted between July and November 2020 using an electronic questionnaire to collect information about the practice of SM and the associated sociodemographic characteristics, health perception, and lifestyle. We collected 1,553 responses and identified a prevalence of 14.9% for SM. The risk factors for SM were earning between BRL 2,101 and BRL 5,250, studying at a public university, and studying a distance undergraduate course. The protective factors were age above 30 years, female sex, working or participating in internships, occasionally recommending their own medications to other people, and worsening health during the pandemic. The main drugs or products used were ivermectin, vitamins C and D, tea, azithromycin, zinc, and propolis. Our data could help in the development of health education measures to reduce SM among undergraduate students and guide the population regarding the risks of this practice.

Polydatin as a therapeutic alternative for central nervous system disorders: A systematic review of animal studies.

Polydatin, or piceid, is a natural stilbene found in grapes, peanuts, and wines. Polydatin presents pharmacological activities, including neuroprotective properties, exerting preventive and/or therapeutic effects in central nervous system (CNS) disorders. In the present study, we summarize and discuss the neuroprotective effects of polydatin in CNS disorders and related pathological conditions in preclinical animal studies. A systematic review was performed by searching online databases, returning a total of 110 records, where 27 articles were selected and discussed here. The included studies showed neuroprotective effects of polydatin in experimental models of neurological disorders, including cerebrovascular disorders, Parkinson's disease, traumatic brain injuries, diabetic neuropathy, glioblastoma, and neurotoxicity induced by chemical agents. Most studies were focused on stroke (22.2%) and conducted in male rodents. The intervention protocol with polydatin was mainly acute (66.7%), with postdamage induction treatment being the most commonly used regimen (55.2%). Overall, polydatin ameliorated behavioral dysfunctions and/or promoted neurological function by virtue of its antioxidant and antiinflammatory properties. In summary, this review offers important scientific evidence for the neuroprotective effects and distinct pharmacological mechanisms of polydatin that not only enhances the present understanding but is also useful for the development of future preclinical and clinical investigations.

Probucol Protects Neuronal Cells Against Peroxide-Induced Damage and Directly Activates Glutathione Peroxidase-1.

Experimental evidence has shown that probucol, a hypocholesterolemic agent, is also able to increase glutathione peroxidase (GPx) activity. However, there is a lack of knowledge about the mechanism(s) involved in this event. In this study, in vitro experiments with purified GPx1 from bovine erythrocytes and cultured SH-SY5Y neuroblastoma cells, as well as in silico studies with GPx1, were performed in order to elucidate mechanisms mediating the stimulatory effect of probucol on GPx activity and to investigate the relevance of this event in terms of susceptibility against peroxide-induced cytotoxicity. In vitro experiments with purified GPx1 showed a direct stimulatory effect of probucol on the activity of GPx1, which was related to an increase in Vmax with no changes in KM. Probucol also increased GPx activity in cultured SH-SY5Y neuroblastoma cells, while the levels of GPx1 expression were not changed, corroborating the results found with the purified enzyme. In addition, probucol rendered SH-SY5Y cells more resistant to hydroperoxide-induced cytotoxicity, and this event was abolished in GPx1 knocked-down cells. In silico studies with GPx1 pointed to a potential binding site for probucol at the close vicinity of the GSH pocket. Collectively, the results presented herein indicate that GPx1 plays a central role in the probucol-induced protective effects against peroxide toxicity. This highlights a novel target (GPx1) and a new mechanism of action (direct activation) for an "old drug." The relevance of such results for in vivo conditions deserves further investigation.

Synthesis and antitumoral activity of novel analogues monastrol-fatty acids against glioma cells.

Monastrol is a small cell-permeable heterocyclic molecule that is recognized as an inhibitor of mitotic kinesin Eg5. Heterocyclic-fatty acid derivatives are a new class of compounds with a broad range of biological activities. This work describes a comparative study of the in vitro antitumoral activity of a series of new long-chain monastrol analogues against rat glioblastoma cells. The novel analogues C6-substituted monastrol and oxo-monastrol were synthesized via Biginelli multicomponent condensation of fatty ß-ketoester in good yields using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Following synthesis, their in vitro antitumoral activities were investigated. Notably, all analogues tested were active against rat glioblastoma cells. Superior activity was observed by analogues derived from palmitic and stearic fatty acid chains; these compounds were the most potent molecules, showing 13-fold higher potency than monastrol with IC50 values of 5.11 and 6.85 µM, respectively. These compounds could provide promising new lead derivatives for more potent antitumor drugs.

Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.

Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.

Green tea extract reverses endothelial dysfunction and reduces atherosclerosis progression in homozygous knockout low-density lipoprotein receptor mice.

The aim of this study was to evaluate the effects of green tea extract (GTE) administration on vascular reactivity and atherosclerosis progression in low-density lipoprotein receptor knockout mice. We hypothesized that GTE intake may ameliorate atherosclerosis by improving endothelial dysfunction. Animals (n = 12 per group) were fed a hypercholesterolemic diet and received either water or GTE at a dose of 50, 100, or 300 mg/kg once a day by gavage (100 µL/10 g weight). After 4 weeks, atherosclerosis extension and vascular reactivity were evaluated in the aorta, and the levels of lipids, monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor α were measured in the plasma. Administration of GTE at a dose of 50 mg/kg significantly decreased the area of atherosclerotic lesions by 35%, improved the vascular reactivity in the isolated thoracic aorta, and lowered the plasma levels of both MCP-1 and triglycerides. Delivery of 100 mg/kg of GTE only promoted vasocontraction and vasorelaxation (P < .05), whereas a dose of 300 mg/kg was ineffective. Maximum contraction and relaxation negatively correlated with the lesion area (r = -0.755 and -0.767, respectively), whereas the plasma levels of MCP-1 and triglycerides positively correlated with plaque size (r = 0.549 and 0.421, respectively). In summary, our results supported the hypothesis that administration of GTE at low doses may contribute to a decrease in atherosclerosis progression by reversing endothelial dysfunction.