ABSTRACT
The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.
Subject(s)
Docetaxel , Prostatic Neoplasms , Male , Docetaxel/pharmacology , Docetaxel/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms/metabolism , Humans , Animals , Emulsions , Cell Line, Tumor , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice , Lipids/blood , Disease Progression , Exercise , Nanoparticles/chemistry , Cell Proliferation/drug effects , Physical Conditioning, AnimalABSTRACT
The objective of this study was to evaluate the effects of different doses of 2,4-dichlorophenoxyacetic herbicide in rat hearts. Exposure was through rat food that was nebulized with the herbicide. Thirty adult male Wistar rats (200-300 g) were used. The diet was exposed to 2,4-D in two different doses (CG: control group 10 ml distilled water; LCG: low concentration group 3.71 × 10-3 g.ia/ha diluted in 10 ml saline at 0.9% and HCG: High concentration group 9.28 × 10-3 g.ia/ha diluted in 10 ml 0.9% saline). After 6 months of exposure, blood samples were collected for CKMB evaluation, and left ventricular fragments were analyzed by histological evaluation, fibrosis measurements, fractal dimension and immunohistochemistry (BAX, Bcl2, TNF-α and NF-kB). There were no significant changes in CK-MB concentration, histological parameters, fibrosis measurements and fractal dimension. Long-term oral consumption of food nebulized by the herbicide 2,4-D promoted an increase in BAX, Bcl-2/BAX, and cytoplasmic NF-kB in the nuclear area of the group that received the highest dose of the herbicide. This suggests that the herbicide induces cardiotoxicity.