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1.
Curr Pharm Biotechnol ; 22(5): 636-645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32679017

RESUMO

BACKGROUND: Cancer is one of the leading cause of death worldwide. Besides current therapies and treatments to counter cancer, new alternatives are required to diminish the cell proliferation of oncogenic processes. METHODS: One of the most promissory therapy includes the use of blue scorpion venom as a specific cytotoxic agent to kill tumoral cells, including Glioblastoma multiforme. OBJECTIVES: We show evidence of the cytotoxic effect of blue scorpion venom in a cellular model of Glioblastoma multiforme. RESULTS: Our results demonstrate that 50 µg/ml of scorpion venom is capable to diminish the viability of Glioblastoma populations. CONCLUSION: It is possible that the action mechanism could be associated with a loss of membrane integrity. Additionally, some metalloproteinases as MMP2 and MMP9 may also participate in the potential action mechanism.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Venenos de Escorpião/farmacologia , Animais , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Escorpiões
2.
Curr Pharm Des ; 25(45): 4737-4746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31957605

RESUMO

Traumatic Brain Injury is considered one of the most prevalent causes of death around the world; more than seventy millions of individuals sustain the condition per year. The consequences of traumatic brain injury on brain tissue are complex and multifactorial, hence, the current palliative treatments are limited to improve patients' quality of life. The subsequent hemorrhage caused by trauma and the ongoing oxidative process generated by biochemical disturbances in the in the brain tissue may increase iron levels and reactive oxygen species. The relationship between oxidative damage and the traumatic brain injury is well known, for that reason, diminishing factors that potentiate the production of reactive oxygen species have a promissory therapeutic use. Iron chelators are molecules capable of scavenging the oxidative damage from the brain tissue and are currently in use for ironoverload- derived diseases. Here, we show an updated overview of the underlying mechanisms of the oxidative damage after traumatic brain injury. Later, we introduced the potential use of iron chelators as neuroprotective compounds for traumatic brain injury, highlighting the action mechanisms of iron chelators and their current clinical applications.


Assuntos
Lesões Encefálicas Traumáticas , Quelantes de Ferro/uso terapêutico , Ferro , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio
3.
CNS Neurol Disord Drug Targets ; 17(10): 743-756, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30179148

RESUMO

BACKGROUND & OBJECTIVE: Regulation of composition, volume and turnover of fluids surrounding the brain and damp cells is vital. These fluids transport all substances required for cells and remove the unwanted materials. This regulation tends to act as barrier to prevent free exchange of materials between the brain and blood. There are specific mechanisms concerned with fluid secretion of the controlled composition of the brain, and others responsible for reabsorption eventually to blood and the extracellular fluid whatever their composition is. The current view assumes that choroidal plexuses secrete the major part of Cerebrospinal Fluid (CSF), while the Blood-Brain Barrier (BBB) has a much less contribution to fluid production, generating Interstitial Fluid (ISF) that drains to CSF. The skull is a rigid box; thereby the sum of volumes occupied by the parenchyma with its ISF, related connective tissue, the vasculature, the meninges and the CSF must be relatively constant according to the Monroe-Kellie dogma. This constitutes a formidable challenge that normal organisms surpass daily. The ISF and CSF provide water and solutes influx and efflux from cells to these targeted fluids in a quite precise way. Microvessels within the parenchyma are sufficiently close to every cell where diffusion areas for solutes are tiny. Despite this, CSF and ISF exhibit very similar compositions, but differ significantly from blood plasma. Many hydrophilic substances are effectively prevented from the entry into the brain via blood, while others like neurotransmitters are extremely hindered from getting out of the brain. Anatomical principle of the barrier and routes of fluid transfer cannot explain the extraordinary accuracy of fluids and substances needed to enter or leave the brain firmly. There is one aspect that has not been deeply analyzed, despite being prevalent in all the above processes, it is considered a part of the CSF and ISF dynamics. This aspect is the energy necessary to propel them properly in time, form, space, quantity and temporality. CONCLUSION: The recent hypothesis based on glucose and ATP as sources of energy presents numerous contradictions and controversies. The discovery of the unsuspected intrinsic ability of melanin to dissociate and reform water molecules, similar to the role of chlorophyll in plants, was confirmed in the study of ISF and CSF biology.


Assuntos
Transporte Biológico/fisiologia , Barreira Hematoencefálica/fisiologia , Encéfalo/fisiologia , Líquido Cefalorraquidiano/metabolismo , Melaninas/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/metabolismo , Plexo Corióideo/metabolismo , Plexo Corióideo/ultraestrutura , Homeostase , Humanos , Melaninas/química
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