RESUMO
Isotretinoin is an analogue of vitamin A and by suppressing the sebaceous glands it is often prescribed in cases of severe acne treatment. The treatment for the average patient is carried out during two to ten months. This study was designed to investigate liver structure, hepatic enzyme levels and the stress oxidative parameter after isotretinoin treatment during a similar period and using the dosages of 1 mg/kg and another one of 10 mg/kg in young male Wistar rats. We have analyzed the blood serum biochemical levels to determine hepatic function and lipid peroxidation, hepatic tissue levels of hepatic enzymes, histology and ultrastructure. The groups receiving 1 mg/kg were not altered after treatment. Their ultrastructure showed a metabolically more active organ after treatment with 10 mg/kg, in which there was an increase in the area occupied by mitochondria and rough reticulum in electron transmission images. The group that received 10 mg/kg also showed increased alkaline phosphatase, decreased high density lipoprotein and low density lipoprotein. The changes observed with the 10 mg/kg dose were not conclusive for liver damage, because of the lack of histological structural modifications and the few biochemical alterations. The 1 mg/kg dose showed a liver responding to some stimuli but without profound alterations. So, we confirm that the proposed protocol with 1mg/kg or 10 mg/kg isotretinoin did not cause important biochemical and histological disfunctions for male Wistar rat livers.
Assuntos
Fármacos Dermatológicos/toxicidade , Isotretinoína/toxicidade , Fígado/efeitos dos fármacos , Animais , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Fígado/citologia , Fígado/ultraestrutura , Masculino , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
In the context of developing a new natural product-based cosmetic, the in vitro efficacy and safety evaluations of a complex botanical mixture based on Eugenia dysenterica leaf hydroalcoholic extract (EDE) (2.5-1000µg/mL) were carried out. Chromatographic analysis demonstrated the presence of the tannin (ellagic acid) and flavonoids (quercetin and gallic acid) which characterize the EDE as a polyphenol-rich mixture. Using HFF-1 fibroblasts, it was shown that EDE promoted cell regeneration after UVA exposure. It also led to the inhibition of the collagenase, elastase and tyrosinase enzymes, which are involved in skin-related disorders. In terms of toxicological evaluation, the EDE was classified as non-phototoxic through the 3T3 Neutral Red Uptake Phototoxicity Test (OECD N° 432, 2004) and non-eye irritant by Bovine Corneal Opacity and Permeability (OECD N° 437, 2013) assay, in conjunction with corneal histomorphometric analysis. Furthermore, the EDE has no skin sensitization potential as demonstrated by a two-out-of-three prediction model [protein-binding/haptenization (OECD N° 442C, 2015), keratinocyte and dendritic cell activations]. In addition, it was shown that the EDE seems to be non-genotoxic through the cytokinesis-block micronucleus assay (OECD N° 487, 2014) using HepG2 cells. When considered together, these findings support the use of EDE botanical mixture in cosmetic/pharmaceutical products.
Assuntos
Cosméticos/química , Cosméticos/toxicidade , Fármacos Dermatológicos/química , Fármacos Dermatológicos/toxicidade , Eugenia/química , Eugenia/toxicidade , Animais , Bovinos , Células Cultivadas , Misturas Complexas , Qualidade de Produtos para o Consumidor , Córnea/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Dermatite Fototóxica , Humanos , Interleucina-18/metabolismo , Irritantes/toxicidade , Queratinócitos/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/químicaRESUMO
Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230-250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug.