In Vitro Cytotoxic Effects and Mechanisms of Action of Eleutherine Isolated from Eleutherine plicata Bulb in Rat Glioma C6 Cells.

Gliomas are the most common primary malignant brain tumors in adults, and have a poor prognosis, despite the different types of treatment available. There is growing demand for new therapies to treat this life-threatening tumor. Quinone derivatives from plants have received increased interest as potential anti-glioma drugs, due to their diverse pharmacologic activities, such as inhibiting cell growth, inflammation, tumor invasion, and promoting tumor regression. Previous studies have demonstrated the anti-glioma activity of Eleutherine plicata, which is related to three main naphthoquinone compounds-eleutherine, isoeleutherine, and eleutherol-but their mechanism of action remains elusive. Thus, the aim of this study was to investigate the mechanism of action of eleutherine on rat C6 glioma. In vitro cytotoxicity was evaluated by MTT assay; morphological changes were evaluated by phase-contrast microscopy. Apoptosis was determined by annexin V-FITC-propidium iodide staining, and antiproliferative effects were assessed by wound migration and colony formation assays. Protein kinase B (AKT/pAKT) expression was measured by western blot, and telomerase reverse transcriptase mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Eleutherine reduced C6 cell proliferation in a dose-dependent manner, suppressed migration and invasion, induced apoptosis, and reduced AKT phosphorylation and telomerase expression. In summary, our results suggest that eleutherine has potential clinical use in treating glioma.

Chickens treated with a nitric oxide inhibitor became more resistant to Plasmodium gallinaceum infection due to reduced anemia, thrombocytopenia and inflammation.

Malaria is a serious infectious disease caused by parasites of the Plasmodium genus that affect different vertebrate hosts. Severe malaria leads to host death and involves different pathophysiological phenomena such as anemia, thrombocytopenia and inflammation. Nitric oxide (NO) is an important effector molecule in this disease, but little is known about its role in avian malaria models. Plasmodium gallinaceum-infected chickens were treated with aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase, to observe the role of NO in the pathogenesis of this avian model. AG increased the survival of chickens, but also induced higher parasitemia. Treated chickens demonstrated reduced anemia and thrombocytopenia. Moreover, erythrocytes at different stages of maturation, heterophils, monocytes and thrombocytes were infected by Plasmodium gallinaceum and animals presented a generalized leucopenia. Activated leukocytes and thrombocytes with elongated double nuclei were observed in chickens with higher parasitemia; however, eosinophils were not involved in the infection. AG reduced levels of hemozoin in the spleen and liver, indicating lower inflammation. Taken together, the results suggest that AG reduced anemia, thrombocytopenia and inflammation, explaining the greater survival rate of the treated chickens.

Global Human Threat: The Potential Synergism between Mercury Intoxication and COVID-19.

The COVID-19 pandemic affected billions of people worldwide, and exposure to toxic metals has emerged as an important risk factor for COVID-19 severity. Mercury is currently ranked as the third toxic substance of global concern for human health, and its emissions to the atmosphere have increased globally. Both COVID-19 and mercury exposure present a high prevalence in similar regions: East and Southeast Asia, South America and Sub-Saharan Africa. Since both factors represent a multiorgan threat, a possible synergism could be exacerbating health injuries. Here, we discuss key aspects in mercury intoxication and SARS-CoV-2 infection, describing the similarities shared in clinical manifestations (especially neurological and cardiovascular outcomes), molecular mechanisms (with a hypothesis in the renin-angiotensin system) and genetic susceptibility (mainly by apolipoprotein E, paraoxonase 1 and glutathione family genes). Literature gaps on epidemiological data are also highlighted, considering the coincident prevalence. Furthermore, based on the most recent evidence, we justify and propose a case study of the vulnerable populations of the Brazilian Amazon. An understanding of the possible adverse synergism between these two factors is crucial and urgent for developing future strategies for reducing disparities between developed and underdeveloped/developing countries and the proper management of their vulnerable populations, particularly considering the long-term sequelae of COVID-19.