Efficacy and safety of nanoparticles of glibenclamide and organomodified layered double hydroxides in diabetics rats.

Glibenclamide (GB) is an important drug in the treatment of type II diabetes mellitus (DM II); however, its low solubility causes variability in its oral bioavailability, negatively affecting the pharmacological treatment. Nanoparticles (NP) of GB and organophilized Layered Double Hydroxide (LDH) were developed to improve oral bioavailability and tested in streptozotocin-induced diabetic rats to evaluate therapeutic efficacy and safety. Blood glucose was measured for 12 h or after 28 days of treatment. In addition, body weight, water and feed consumption, hematological, biochemistry and morphological parameters and markers of oxidative stress were determined. After the treatment, GB with LDH normalized the blood glucose level, indicating a better release profile. Water and feed intake and body weight of animals treated with GB and GB with LDH were closer to the normoglycemic group and did not indicate signs of toxicity of the nanoparticles. The biochemical, hematological and histological results also showed no significant changes related to nanotoxicity. The combination of GB with LDH proved to be critical in the oxidative balance, as it reduced the oxidative stress of vascular tissue. In conclusion, NPs are a potential controlled release system for the treatment of DM II.

Acute restraint stress induces an imbalance in the oxidative status of the zebrafish brain.

The zebrafish (Danio rerio) has become an emergent model organism for translational approaches focused on the neurobiology of stress due to its genetic, neuroanatomical, and histological similarities with mammalian systems. However, despite the increasing number of studies using zebrafish, reports examining the impact of stress on relevant neurochemical parameters are still elementary when compared to studies using rodents. Additionally, it is important to further validate this model organism by comparing its stress response with those described in other species. Here, we evaluated the effects of an acute restraint stress (ARS) protocol on oxidative stress-related parameters in the zebrafish brain. Our data revealed that ARS significantly decreased catalase activity without altering the activity of superoxide dismutase. Oxidative stress was also indicated by increased levels of lipid peroxides. ARS significantly increased the levels of non-protein thiols, although significant changes in total reduced sulfhydryl content were not detected. These results suggest that ARS is an interesting strategy for evaluating the mechanisms underlying the neurochemical basis of the oxidative profile triggered by acute stressors in the zebrafish brain. Furthermore, this protocol may be suitable for screening new compounds with protective properties against oxidative stress, which plays an increasingly important role in many psychiatric disorders.