Avaliação da toxicidade cutânea in vivo e predição computacional de propriedades e potencial terapêutico do óleo de tucumã (Astrocaryum vulgare Mart.)

Abstract

The Amazon region is known for presenting biological diversity, cultural richness and a characteristic climate, which favors the cultivation of fruits typical of the region, such as tucumã (Astrocaryum vulgare Mart.). The oil obtained from tucumã has a valuable composition and great potential for use in the formulation of cosmetic products and medicines. There are studies that evaluate tucumã oil (TO) used orally, but the effects of its use with skin application are little known. Thus, the objective of this work was to evaluate the acute cutaneous toxicity and repeated doses of TO in Wistar rats. In addition to identifying the major compounds of TO, perform computational prediction of pharmacokinetic, toxicological parameters and biological activities of these compounds, defining a possible therapeutic target and perform docking and molecular dynamics studies to evaluate the effect and possible mechanism of action of TO on this target. To assess acute toxicity in rats, the oil was applied to the skin in a single dose of 2000 mg/kg and the animals were observed for 14 days. To determine the toxicity of repeated doses, the oil was applied to three groups of rats in increasing doses of 250, 500 and 1000 mg/kg for 28 days. Body weight and food consumption were monitored and blood, liver, kidney and skin samples were collected for evaluation. The analysis of the TO composition was performed by gas chromatography with mass spectrometry and the properties of the identified compounds were predicted using computational methodologies. Molecular docking was performed between these compounds and proteins involved in the pathogenesis of atopic dermatitis (PDE4A, IL4Rα, STAT3, JAK1 and PPARγ), and validated by molecular dynamics. The main compounds of TO are fatty acids and glycerides, especially oleic acid, palmitic acid, trilaurin and monoolein. Some of these compounds may have mutagenic and carcinogenic effects, but have not indicated acute oral or hepatic, cardiac or reproductive toxicity. PDE4A, STAT3 and JAK1 proteins showed greater interaction with monoolein in the docking study, but these interactions were not seen in molecular dynamics. The PPARγ protein showed promising interaction with trilaurin in both simulations. Regarding in vivo experiments, the single application of TO did not cause hematological or biochemical changes, nor skin irritation or corrosion or macroscopic changes in the organs. Daily application for 28 days also did not generate significant changes, except erythema on the skin of treated animals, which was more pronounced at higher doses and resolved spontaneously. TO can be classified as having low acute toxicity and does not cause systemic toxicity, but local toxicity may be associated with its use, depending on the dose. Computational studies highlight OT as a source of compounds with potential topical application. Trilaurin stands out as a promising candidate for the treatment of atopic dermatitis, in line with the traditional and scientific applications of tucumã. However, further investigation of the mutagenic and carcinogenic effects of OT and definition of a dose that is safe and effective is necessary.