Cytotoxicity induced by carbon nanotubes in experimental malignant glioma.

Despite multiple advances in the diagnosis of brain tumors, there is no effective treatment for glioblastoma. Multiwalled carbon nanotubes (MWCNTs), which were previously used as a diagnostic and drug delivery tool, have now been explored as a possible therapy against neoplasms. However, although the toxicity profile of nanotubes is dependent on the physicochemical characteristics of specific particles, there are no studies exploring how the effectivity of the carbon nanotubes (CNTs) is affected by different methods of production. In this study, we characterize the structure and biocompatibility of four different types of MWCNTs in rat astrocytes and in RG2 glioma cells as well as the induction of cell lysis and possible additive effect of the combination of MWCNTs with temozolomide. We used undoped MWCNTs (labeled simply as MWCNTs) and nitrogen-doped MWCNTs (labeled as N-MWCNTs). The average diameter of both pristine MWCNTs and pristine N-MWCNTs was ~22 and ~35 nm, respectively. In vitro and in vivo results suggested that these CNTs can be used as adjuvant therapy along with the standard treatment to increase the survival of rats implanted with malignant glioma.

Role of Redox Status in Development of Glioblastoma.

Glioblastoma multiforme (GBM) is a highly aggressive neoplasia, prognosis remains dismal, and current therapy is mostly palliative. There are no known risk factors associated with gliomagenesis; however, it is well established that chronic inflammation in brain tissue induces oxidative stress in astrocytes and microglia. High quantities of reactive species of oxygen into the cells can react with several macromolecules, including chromosomal and mitochondrial DNA, leading to damage and malfunction of DNA repair enzymes. These changes bring genetic instability and abnormal metabolic processes, favoring oxidative environment and increase rate of cell proliferation. In GBM, a high metabolic rate and increased basal levels of reactive oxygen species play an important role as chemical mediators in the regulation of signal transduction, protecting malignant cells from apoptosis, thus creating an immunosuppressive environment. New redox therapeutics could reduce oxidative stress preventing cellular damage and high mutation rate accompanied by chromosomal instability, reducing the immunosuppressive environment. In addition, therapies directed to modulate redox rate reduce resistance and moderate the high rate of cell proliferation, favoring apoptosis of tumoral cells. This review describes the redox status in GBM, and how this imbalance could promote gliomagenesis through genomic and mitochondrial DNA damage, inducing the pro-oxidant and proinflammatory environment involved in tumor cell proliferation, resistance, and immune escape. In addition, some therapeutic agents that modulate redox status and might be advantageous in therapy against GBM are described.

Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats.

All-trans retinoic acid (ATRA) promotes the endogenous expression of both nerve growth factor (NGF) and retinoic acid receptor beta (RAR-ß). We have previously shown that the administration of ATRA partly reverts the damage induced by diabetic neuropathy (DN). In this investigation, we evaluated the effects of vitamin A, a commercial, inexpensive compound of retinoic acid, on the therapy of DN. A total of 70 rats were randomized into 4 groups. Group A was the control, and groups B, C, and D received a total dose of 60 mg/kg streptozotocin intraperitoneally. When signs of DN developed, groups C and D were treated either with vitamin A (20,000 IU) or with ATRA 25 mg/kg for 60 days. Plasma glucose, contents of NGF, thermal and nociceptive tests, and RAR-ß expression were evaluated. All diabetic rats developed neuropathy. The treatment with vitamin A and ATRA reverted similarly the sensorial disturbances, which was associated with increased contents of NGF and RAR-ß expression. Our results indicate that the administration of vitamin A has the same therapeutic effect as ATRA on peripheral neuropathy and suggest its potential therapeutic use in patients with diabetes.