Malaria is a potentially mortal disease caused by parasites of the genus Plasmodium spp. It has a wide distribution in the world and unfortunately there are several factors that make its control ...difficult; among which the development of pharmacological resistance to the different drugs used to treat this disease stands out, which makes it necessary to design new compounds that have an antimalarial effect. Previous studies have shown that vanadium has a broad antiparasitic spectrum and is also safe for the host, so the objective of this research was to evaluate the antimalarial potential of sodium metavanadate (SM) and to analyze the ultrastructural changes in parasites exposed. The method consisted of inoculating CD-1 male mice with Plasmodium yoelii yoelii and administering a 10 mg/kg/day dose of SM orally for 4 days. On the fifth day, whole blood samples were obtained, processed for ultrastructural analysis, and the changes in the different parasite stages were compared against the control. Our results showed that SM decreased parasitemia compared to the group that did not receive treatment and modified the ultrastructure in all parasitic stages because it damaged the membranes, causing alterations mainly in the nucleus and in the mitochondria as well as the loss of cellular organization, which could affect the integrity of these parasites and decrease its viability.
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•Sodium metavanadate decreases parasitemia compared to the group without treatment.•Vanadium causes ultrastructural damage to the membranes of Plasmodium yoelii yoelii.•Vanadium modifies the ultrastructure of the Plasmodium yoelii yoelii nucleus.•Vanadium causes ultrastructural changes to Plasmodium yoelii yoelii mitochondria.
Environmental pollution is a worldwide problem recognized by the World Health Organization as a major health risk factor that affects low-, middle- and high-income countries. Suspended particulate ...matter is among the most dangerous pollutants, since it contains toxicologically relevant agents, such as metals, including vanadium. Vanadium is a transition metal that is emitted into the atmosphere especially by the burning of fossil fuels to which dwellers are exposed. The objective of this literature review is to describe the toxic effects of vanadium and its compounds when they enter the body by inhalation, based especially on the results of a murine experimental model that elucidates the systemic effects that vanadium has on living organisms. To achieve this goal, we reviewed 85 articles on the relevance of vanadium as a component of particulate matter and its toxic effects. Throughout several years of research with the murine experimental model, we have shown that this element generates adverse effects in all the systems evaluated, because it causes immunotoxicity, hematotoxicity, neurotoxicity, nephrotoxicity and reprotoxicity, among other noxious effects. The results with this experimental model add evidence of the effects generated by environmental pollutants and increase the body of evidence that can lead us to make more intelligent environmental decisions for the welfare of all living beings.
The onset of Alzheimer's disease (AD) is associated with the presence of neurofibrillary pathology such as amyloid β (Aβ) plaques. Different therapeutic strategies have focused on the inhibition of ...Aβ aggregate formation; these pathological structures lead to neuronal disorder and cognitive impairment. Fullerene C
60
has demonstrated the ability to interact and prevent Aβ fibril development; however, its low solubility and toxicity to cells remain significant problems. In this study, we synthesized, characterized and compared diethyl fullerenemalonates and the corresponding sodium salts, adducts of C
60
bearing 1 to 3 diethyl malonyl and disodium malonyl substituents to evaluate the potential inhibitory effect on the aggregation of Aβ
42
and their biocompatibility. The dose-dependent inhibitory effect of fullerenes on Aβ
42
aggregation was studied using a thioflavin T fluorescent assay, and the IC
50
value demonstrated a low range of fullerene concentration for inhibition, as confirmed by electron microscopy. The exposure of neuroblastoma to fullerenemalonates showed low toxicity, primarily in the presence of the sodium salt-adducts. An isomeric mixture of bisadducts, trisadducts and a
C
3
-symetrical trisadduct demonstrated the highest efficacy among the tests.
In silico
calculations were performed to complement the experimental data, obtaining a deeper understanding of the Aβ inhibitory mechanism; indicating that
C
3
-symetrical trisadduct interacts mainly with 1D to 16K residues of Aβ
42
peptide. These data suggest that fullerenemalonates require specific substituents designed as sodium salt molecules to inhibit Aβ fibrillization and perform with low toxicity. These are promising molecules for developing future therapies involving Aβ aggregates in diseases such as AD and other types of dementia.
Synthesis of new non toxic nanomaterials, with high anti-amyloid fibrils formation effect,
in vitro
and
in silico
.
is a fern documented in ethnobotanical records for its use in Mexican traditional medicine to treat gastric disorders and mouth ulcers. Consequently, conducting biological and pharmacological assays ...is crucial to validate the therapeutic efficacy of this plant within the context of traditional medicine. In the present study, we investigated the biological activity of extracts and fractions obtained from
organs against bacteria (
,
,
,
,
,
,
and
using in vitro models. The precipitate fraction obtained from the frond methanolic extract showed significant antibacterial activity (minimal inhibitory concentration MIC 120 µg/mL) against the
strain and was effective against both Gram-positive and Gram-negative bacteria. The hexane fraction also obtained from frond methanolic extract, showed a trichomonacidal effect with an IC
of 82.8 μg/mL and a low cytotoxic effect. Hsf6 exhibited the highest activity against
, and the GC-MS analysis revealed that the predominant compound was 16-pregnenolone. The remaining identified compounds were primarily terpene-type compounds.
During Toxoplasma gondii chronic infection, certain internal factors that trigger the proliferation of neural progenitor cells (NPCs), such as brain inflammation, cell death, and changes in cytokine ...levels, are observed. NPCs give rise to neuronal cell types in the adult brain of some mammals. NPCs are capable of dividing and differentiating into a restricted repertoire of neuronal and glial cell types. In this study, the proliferation of NPCs was evaluated in CD-1 adult male mice chronically infected with the T. gondii ME49 strain. Histological brain sections from the infected mice were evaluated in order to observe T. gondii tissue cysts. Sagittal and coronal sections from the subventricular zone of the lateral ventricles and from the subgranular zone of the hippocampal dentate gyrus, as well as sagittal sections from the rostral migratory stream, were obtained from infected and non-infected mice previously injected with bromodeoxyuridine (BrdU). A flotation immunofluorescence technique was used to identify BrdU+ NPC. The scanning of BrdU+ cells was conducted using a confocal microscope, and the counting was performed with ImageJ® software (version 1.48q). In all the evaluated zones from the infected mice, a significant proliferation of the NPCs was observed when compared with that of the control group. We concluded that chronic infection with T. gondii increased the proliferation of NPCs in the three evaluated zones. Regardless of the role these cells are playing, our results could be useful to better understand the pathogenesis of chronic toxoplasmosis.
(Pc) is a fern that, according to ethnobotanical records, is used in Mexican traditional medicine to treat gastrointestinal ailments. Recent reports indicate that the hexane fraction (Hf) obtained ...from Pc methanolic frond extract affects
tachyzoite viability in vitro; therefore, in the present study, the activity of different Pc hexane subfractions (Hsf) obtained by chromatographic methods was evaluated in the same biological model. Gas chromatography/mass spectrometry (GC/MS) analysis was carried out for hexane subfraction number one (Hsf1), as it showed the highest anti-
activity with a half-maximal inhibitory concentration (IC
) of 23.6 µg/mL, a 50% cytotoxic concentration (CC
) of 398.7 µg/mL in Vero cells, and a selective index (SI) of 16.89. Eighteen compounds were identified by Hsf1 GC/MS analysis, with the majority being fatty acids and terpenes. Hexadecanoic acid, methyl ester was the most commonly found compound (18.05%) followed by olean-13(18)-ene, 2,2,4a,8a,9,12b,14a-octamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,12,12a,12b,13,14,14a,14b-eicosahydropicene, and 8-octadecenoid acid, methyl ester, which were detected at 16.19%, 12.53%, and 12.99%, respectively. Based on the mechanisms of action reported for these molecules, Hsf1 could exert its anti-
activity mainly on
lipidomes and membranes.
Parasitic infections are a public health problem since they have high morbidity and mortality worldwide. In parasitosis such as malaria, leishmaniasis and trypanosomiasis it is necessary to develop ...new compounds for their treatment since an increase in drug resistance and toxic effects have been observed. Therefore, the use of different compounds that couple vanadium in their structure and that have a broad spectrum against different parasites have been proposed experimentally.
Report the mechanisms of action exerted by vanadium in different parasites.
In this review, some of the targets that vanadium compounds have were identified and it was observed that they have a broad spectrum against different parasites, which represents an advance to continue investigating therapeutic options.
•Vanadium compounds damage the parasitic genetic material.•Vanadium inhibits enzymes and causes dysfunction in the mitochondria of parasites.•Vanadium could contribute to the immune response against parasites.•Vanadium modifies the morphology of parasites and increases reactive oxygen species.•Vanadium compounds may alter the life cycle of parasites.
Malaria continues to be a major global health problem, and over 40% of the world's population is at risk. Severe or complicated malaria is defined by clinical or laboratory evidence of vital organ ...dysfunction, including dysfunction of the central nervous system (CNS). The pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (BBB) that protects the CNS against chemical insults. Historically, the BBB has received more attention in the pathogenesis of malaria than have the cerebrospinal fluid-brain barrier (CSFBB) and ependymal cells. This perspective may be misguided because, in the context of disease or toxicity, the CSFBB is more vulnerable to many foreign invaders than are the capillaries. Given the lack on studies of the damage to the CSFBB and ependymal epithelium in experimental murine malaria, the present study evaluated morphological changes in the ependymal cells of CD-1 male mice infected with lethal Plasmodium yoelii yoelii (Pyy) via histopathology and scanning electron microscopy (SEM). Samples were taken two, four and six days post-infection (PI). No lesions were observed upon the initial infection. By the fourth day PI, fourth ventricle ependymal samples exhibited disruptions and roughened epithelia. More severe injuries were observed at six days PI and included thickened cilia and deep separations between the ependymal intercellular spaces. In some of the analyzed areas, the absence of microvilli and cell layer detachment were observed, and some areas exhibited blebbing surfaces. The ependymal cell lesions observed in the CD1 male mice infected with lethal Pyy seemed to facilitate the paracellular permeability of the CSFBB and consequently promote the access of inflammatory mediators and toxic molecules through the barrier, which resulted in damage to the brain tissue. Understanding the mechanism of ependymal disruption during lethal murine malaria could help to elucidate the local and systemic factors that are involved in the pathogenesis of the disease and may provide essential clues for the prevention and treatment of complicated human malaria.
BACKGROUNDMalaria is a parasitic disease with the highest morbidity and mortality worldwide. Unfortunately, during the last decades, the causal agent, Plasmodium spp., has developed resistance to ...chloroquine and artemisinin. For this reason, metallic compounds have been proposed as an optional treatment since they have shown a potential antimalarial effect with diverse action mechanisms in the parasite and the host. OBJECTIVETo show the possible targets of metallic compounds in Plasmodium spp. CONCLUSIONThe metallic compounds are an option attractive to treatment for the malaria, for its low cost and its great activity to reduce parasitemia; however is necessary more studies principally in vivo in order to know the interactions that it can have in an experimental model.
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