Influence of NSAIDs and methotrexate on CD73 expression and glioma cell growth.

Glioblastoma (GBM) is the most malignant and deadly brain tumor. GBM cells overexpress the CD73 enzyme, which controls the level of extracellular adenosine, an immunosuppressive molecule. Studies have shown that some nonsteroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) have antiproliferative and modulatory effects on CD73 in vitro and in vivo. However, it remains unclear whether the antiproliferative effects of MTX and NSAIDS in GBM cells are mediated by increases in CD73 expression and adenosine formation. The aim of this study was to evaluate the effect of the NSAIDs, naproxen, piroxicam, meloxicam, ibuprofen, sodium diclofenac, acetylsalicylic acid, nimesulide, and ketoprofen on CD73 expression in GBM and mononuclear cells. In addition, we sought to understand whether the effects of MTX may be mediated by CD73 expression and activity. Cell viability and CD73 expression were evaluated in C6 and mononuclear cells after exposure to NSAIDs. For analysis of the mechanism of action of MTX, GBM cells were treated with APCP (CD73 inhibitor), dipyridamole (inhibitor of adenosine uptake), ABT-702 (adenosine kinase enzyme inhibitor), or caffeine (P1 adenosine receptor antagonist), before treatment with MTX and AMP, in the presence or not of mononuclear cells. In summary, only MTX increased the expression of CD73 in GBM cells decreasing cells viability by mechanisms independent of the adenosinergic system. Further studies are needed to understand the role of MTX in the GBM microenvironment.

Effects of the ingestion of different kinds of white grape juice (Vitis labrusca) during adolescence on body weight, biochemical parameters and oxidative stress in liver of adult Wistar rats.

The objective of this study was to evaluate the effects of the ingestion of different white grape juices: organic, conventional and conventional grape juice with 5% lemon juice during adolescence on biochemical serum profile and oxidative stress level in liver of adult Wistar rats. The phenolic and vitamin C composition of the juices were evaluated. During 32 days the rats were treated with the juices or oral water (gavage) for at a dose of 7 µL/g body weight. The animals were divided into 4 groups (n = 16/each). In the end, half of the animals received an intraperitoneal CCl4 injection of 3.0 mL/kg; the other ones received mineral oil. After euthanasia, biochemical parameters were evaluated in serum and oxidative stress in the liver. It is possible to emphasize that the juices have different phenolic and vitamin C contents. The juice consumption didn't alter the weight body and biochemical parameters in adult life.