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BACKGROUND: Obesity is a metabolic disease that affects many individuals around the world, related to imbalance between energy consumption and expenditure, which can lead to comorbidities. A healthy diet can significantly contribute to the prevention or treatment of this condition. Jabuticaba is an emerging fruit presenting a wide range of bioactive compounds and is being extensively studied due to its effects on lipid metabolism. The aim of this study was to evaluate the jabuticaba extract in the anxious-like behavior and in the lipid and oxidative metabolism in the context of obesity. METHODS: Forty male Wistar rats divided into five groups were used. The animals received a standard diet and/or a hypercaloric diet and after 60 days of induction, interventions were carried out with jabuticaba extract (5% and 10%) via gavage for 30 days. RESULTS: It can be observed that the jabuticaba extract was able to reverse the anxious behavior observed in obese animals and modulate parameters of lipid and oxidative metabolism. We observed a reduction in cholesterol and triglyceride levels compared to obese animals. Furthermore, we observed an improvement in oxidative parameters, with a reduction in protein carbonylation in the liver and modulation of antioxidant enzymes such as superoxide dismutase and catalase. Contrary to expectations, we did not observe changes in leptin, adiponectin and tumor necrosis factor alpha (TNF-α) levels. CONCLUSION: Our work demonstrates that jabuticaba extract can improve metabolic, oxidative and behavioral changes in animals with obesity. © 2024 Society of Chemical Industry.
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PURPOSE: We investigated the impact of nanoformulations on the dose-exposure-response relationship of clozapine (CZP), a low-solubility antipsychotic with serious adverse effects, using a popPK/PD approach. METHODS: We evaluated the pharmacokinetics and PK/PD profiles of three coated polymeric CZP-loaded nanocapsules functionalized with polysorbate 80 (NCP80), polyethylene glycol (NCPEG), and chitosan (NCCS). Data on in vitro CZP release by dialysis bag, plasma pharmacokinetic profiles in male Wistar rats (n = 7/group, 5 mg kg-1, i.v.), and percentage of head movements in a stereotyped model (n = 7/group, 5 mg kg-1, i.p.) were integrated using a sequential model building approach (MonolixSuiteTM-2020R1-Simulation Plus). RESULTS: A base popPK model developed with CZP solution data collected after the i.v. administration of CZP was expanded to describe the changes in drug distribution caused by nanoencapsulation. Two additional compartments were inserted into the NCP80 and NCPEG models, and a third compartment was included in the NCCS model. The nanoencapsulation showed a decrease in the central volume of distribution for NCCS (V1NCpop = 0.21 mL), while for FCZP, NCP80, and NCPEG, it was ~1 mL. The peripheral distribution volume was higher for the nanoencapsulated groups (19.1 and 129.45 mL for NCCS and NCP80, respectively) than for FCZP. The popPK/PD model showed a formulation-dependent plasma IC50, with 20-, 50-, and 80-fold reductions compared to the CZP solution (NCP80, NCPEG, and NCCS, respectively). CONCLUSION: Our model discriminates the coatings and describes the peculiar PK and PD behavior of nanoencapsulated CZP, especially NCCS, making it an exciting tool for evaluating the preclinical performance of nanoparticles.