RESUMO
There are good evidences suggesting that endoplasmic reticulum (ER) stress can be one of the contributing factors in the development of diabetic retinopathy. The present study was designed to investigate the effect of chemical chaperone 4-phenylbutyric acid (4-PBA) in alleviating the ER stress, and diabetic retinopathy in type 2 diabetic rats. Treatment of diabetic rats with 4-PBA, increased the antioxidant capacity, reduced the levels of lipid peroxidation, organised the state of apoptosis and regulated the ER stress - oxidative activation in retinal tissue. Also there was an improvement in the histological picture of retinal specimens compared to untreated diabetic rats. It was concluded that 4-PBA is a promising therapeutic agent for ER stress diseases such as diabetic retinopathy.
Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Ratos , Animais , Retinopatia Diabética/tratamento farmacológico , Ratos Sprague-Dawley , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse do Retículo Endoplasmático , Apoptose , Estresse OxidativoRESUMO
The present work reports a nanotechnology strategy to prepare a low-viscosity poly(acrylic acid) (PAAc)-based tear substitute with enhanced efficacy and compliance. Specifically, nanogels composed of PAAc and polyvinylpyrrolidone (PVP) were prepared by adapting an ionizing radiation method. For this purpose, different aqueous systems: PVP/PAAc nanoparticulate complexes, PVP/acrylic acid (AAc), N-vinylpyrrolidone (N-VP)/PAAc, and N-VP/AAc were exposed to gamma rays. The dynamic light scattering technique showed that stable nanogels are only produced in a relatively high yield from the PVP/AAc system. Nanogel formation was driven by the hydrogen-bonding complexation between PVP and PAAc (formed in situ) as well as the radiation-induced cross-linking. Transparency, viscosity and mucoadhesiveness of emerged nanogels were optimized by controlling the feed composition and irradiation dose. Furthermore, neutralized nanogels were topically applied in a dry eye model and compared with a PAAc-based commercial tear substitute, namely Vidisic® Gel. The results of Schirmer's test and tear break-up time demonstrated that nanogels prepared from AAc-rich feed solutions at 20 kGy enhanced markedly the dry eye conditions. The histopathological analysis also ensured the competence of PAAc-rich nanogels to completely return the corneal epithelium to its normal state.