Glioblastoma multiforme (GBM) is the worst and most common brain tumor, characterized by high proliferation and invasion rates. Nanoparticles of biodegradable polymers for anticancer drug delivery have attracted interest in recent years since they provide targeted delivery and may overcame the obstacle imposed by blood-brain barrier. Here we investigated the antitumoral effect of ketoprofen-loaded nanocapsules (Keto-NC) treatment on in vitro and in vivo glioma progression. We observed that Keto-NC treatment decreased selectively the cell viability of a panel of glioma cell lines, while did not exhibited toxicity to astrocytes. We further demonstrate that the treatment with sub-therapeutic dose of Keto-NC reduced the in vivo glioma growth as well as reduced the malignity characteristics of implanted tumors. Keto-NC treatment improved the weight, the locomotion/exploration behavior of glioma-bearing rats. Importantly, Keto-NC treatment neither induced mortality or peripheral damage. Finally, Ketoprofen also altered the extracellular nucleotide metabolism of peripheral lymphocytes, suggesting that antiinflammatory effects of ketoprofen could also be associated with the modulation of the adenine nucleotide metabolism in lymphocytes. Data indicate at first time the potential of Keto-NC as a promising therapeutic alterative to GBM treatment.
High levels of methionine (Met) and methionine sulfoxide (MetO) are found in several genetic abnormalities. Oxidative stress is involved in the pathophysiology of many inborn errors of metabolism. However, little is known about the role of oxidative damage in hepatic and renal changes in hypermethioninemia. We investigated the effect of chronic treatment with Met and/or MetO on oxidative stress parameters in liver and kidney, as lipid peroxidation (TBARS), total sulfhydryl content (SH), reactive oxygen species (ROS) and enzymes activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and delta aminolevulinic dehydratase (ALA-D). Serum biochemical parameters were evaluated. Wistar rats were treated daily with two subcutaneous injections of saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1 g/kg) and the association between these (Met plus MetO) from the 6th to the 28th day of life. Our data demonstrated an increase of glucose and urea levels in all experimental groups. Cholesterol (MetO and Met plus MetO) were decreased and triglycerides (MetO) were increased. SOD (MetO and Met plus MetO) and CAT (Met, MetO and Met plus MetO) activities were decreased, while GPx was enhanced by MetO and Met plus MetO treatment in liver. In kidney, we observed a reduction of SH levels, SOD and CAT activities and an increase of TBARS levels in all experimental groups. ROS levels in kidney were increased in MetO and Met plus MetO groups. ALA-D activity was enhanced in liver (MetO and Met plus MetO) and kidney (Met plus MetO). These findings help to understand the pathophysiology of hepatic and renal alterations present in hypermethioninemia.
The aim of the present study was to evaluate the protective effects of blueberry extract on oxidative stress and inflammatory parameters in a model of mania induced by ketamine administration in rats. Male rats were pretreated with blueberry extract (200mg/kg, once a day for 14days), lithium chloride (45mg/kg, mood stabilizer used as a positive control, twice a day for 14days), or vehicle. Between the 8th and 14th days, rats also received an injection of ketamine (25mg/kg) or vehicle. In the 15th day, thirty minutes after ketamine administration the hyperlocomotion of the animals was assessed in the open - field apparatus. Immediately after the behavioral analysis brain and blood were collected for biochemical determinations. ketamine treatment induced hyperlocomotion and oxidative damage in cerebral cortex, hippocampus and striatum such as an increase in lipid peroxidation and a decrease in the antioxidant enzymes activities (superoxide dismutase, catalase e glutatione peroxidase). Ketamine administration also increased the IL-6 levels in serum in rats. Pretreatment of rats with blueberry extract or lithium prevented the hyperlocomotion, pro - oxidant effects and inflammation induced by ketamine. Our findings suggest that blueberry consumption has a neuroprotective potential against behavioral and biochemical dysfunctions induced in a preclinical model that mimic some aspects of the manic behavior.
In this study we investigated the effect of acute and chronic treatment with Met and/or methionine sulfoxide (MetO) on ectonucleotidases and cholinesterases activities from lymphocytes and purine derivatives compounds, C-protein reactive, interleukin-10, interleukin-6, and tumor necrosis factor-α levels in serum of young rats. Adenosine triphosphate hydrolysis was decreased in lymphocytes 1 h after treatment by MetO and Met + MetO. However, adenosine triphosphate and adenosine diphosphate hydrolysis in lymphocytes was increased in the groups MetO and Met + MetO and adenosine deaminase activity was increased in MetO 3 h after the treatment. Acetylcholinesterase activity was increased in lymphocytes after 3 h and 21 days of treatment by MetO and Met + MetO, while serum butyrycholinesterase activity was decreased after 1 h and 21 days of treatment in the same groups. In chronic treatment, interleukin-6 and tumor necrosis factor-α level were increased, while that interleukin-10 level was decreased by Met, MetO, and Met + MetO when compared to control group. C-protein reactive level was increased by MetO and Met + MetO. Adenosine triphosphate and adenosine monophosphate levels were reduced in all amino acids treated groups, while adenosine diphosphate and hypoxanthine were enhanced by MetO and Met + MetO. Adenosine and xanthine were reduced in the MetO group, whereas inosine levels were decreased in the MetO and Met + MetO groups. These findings help to understand the inflammatory alterations observed in hypermethioninemia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.