RESUMEN
Glioblastoma (GBM) is an aggressive form of cancer affecting the Central Nervous System (CNS) of thousands of people every year. Redox alterations have been shown to play a key role in the development and progression of these tumors as Reactive Oxygen Species (ROS) formation is involved in the modulation of several signaling pathways, transcription factors, and cytokine formation. The second-generation oral alkylating agent temozolomide (TMZ) is the first-line chemotherapeutic drug used to treat of GBM, though patients often develop primary and secondary resistance, reducing its efficacy. Antioxidants represent promising and potential coadjutant agents as they can reduce excessive ROS formation derived from chemo- and radiotherapy, while decreasing pharmacological resistance. S-allyl-cysteine (SAC) has been shown to inhibit the proliferation of several types of cancer cells, though its precise antiproliferative mechanisms remain poorly investigated. To date, SAC effects have been poorly explored in GBM cells. Here, we investigated the effects of SAC in vitro, either alone or in combination with TMZ, on several toxic and modulatory endpoints-including oxidative stress markers and transcriptional regulation-in two glioblastoma cell lines from rats, RG2 and C6, to elucidate some of the biochemical and cellular mechanisms underlying its antiproliferative properties. SAC (1-750 µM) decreased cell viability in both cell lines in a concentration-dependent manner, although C6 cells were more resistant to SAC at several of the tested concentrations. TMZ also produced a concentration-dependent effect, decreasing cell viability of both cell lines. In combination, SAC (1 µM or 100 µM) and TMZ (500 µM) enhanced the effects of each other. SAC also augmented the lipoperoxidative effect of TMZ and reduced cell antioxidant resistance in both cell lines by decreasing the TMZ-induced increase in the GSH/GSSG ratio. In RG2 and C6 cells, SAC per se had no effect on Nrf2/ARE binding activity, while in RG2 cells TMZ and the combination of SAC + TMZ decreased this activity. Our results demonstrate that SAC, alone or in combination with TMZ, exerts antitumor effects mediated by regulatory mechanisms of redox activity responses. SAC is also a safe drug for testing in other models as it produces non-toxic effects in primary astrocytes. Combined, these effects suggest that SAC affords antioxidant properties and potential antitumor efficacy against GBM.
RESUMEN
Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.
RESUMEN
Total copper and manganese contents were measured in five rat brain regions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1µl), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace atomic absorption spectrophotometry. Increases in copper content were observad after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152 percent as compared against control values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35 percent vs. control values, but not in all other brain regions analyzed. QUIN-induced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23 percent vs. control, respectively) by pretreatment of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN microinjection. The same protective effect of fizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45 percent vs. control). These findings resemble those changes observed in postmortem Huntington's disease brain and suggest that alterations in regional content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tissue to the neighboring regions of the brain, by action of QUIN on NMDA receptors
Asunto(s)
Ratas , Animales , Ácido Quinolínico/administración & dosificación , Cerebro/metabolismo , Cobre/aislamiento & purificación , Cuerpo Estriado/efectos de los fármacos , Pentobarbital , Ratas Wistar/metabolismo , EspectrofotometríaRESUMEN
Se estudió bioquímicamente la intoxicación experimental por talio en ratas neonatas y sus consecuencias morfológicas en el encéfalo de los animales en desarrollo. Se analizó el contenido de talio en las siguientes regiones del encéfalo: hipocampo, hipotálamo, mesencéfalo, cerebelo y corteza, un día después de la administración del tóxico encontrándose una distrubución homogénea del metal en el encéfalo. Las concentraciones del talio en las regiones citadas es de casi el doble de lo encontrado en el adulto a la misma dosis. Para el estudio histopatológico se utilizaron 20 ratas recién nacidas Cepa Wistar. Cinco quedaron como testigos las 15 restantes fueron inyectadas con una sola dosis de talio a .07 mL de una solución de .32 mg/kg de peso. Se sacrificaron 3 ratas a las 24, 48 y 72 hrs, 3 a los 7 días y 3 a los 51 días. El encéfalo y nervios ciáticos y crural se fijaron en formol al 10 por ciento por 15 días. De los fragmentos de diferentes áreas se hicieron cortes en parafina o congelación de 5 a 7 micras de grosor. Teñidos con anilinas (Masson, Gallego y H-E e impregnaciones argento-áuricas de Río-Hortega modificadas