Avaliação da toxicidade utilizando modelos in vivo e in silico da naringenina nanoencapsulada

Abstract

Naringenin is a flavonoid derived from naringin, considered a glycosylated polyphenol of the flavanone class present in citrus plants such as grapefruit (Citrus paradisi L.). It presents bioactive properties such as anti-inflammatory, antineoplastic, antiatherogenic and antioxidant activity. However, it has low bioavailability, low water solubility and instability that limit its application, hindering its action and absorption in the body. Encapsulation methods such as the solid dispersion technique may be effective in overcoming such negative points of naringenin. It is necessary to assess the degree of safety of nanoencapsulated formulations and, in this context, the meristematic tissue of Allium cepa L. roots presents characteristics that make it an efficient test tool for the assessment of cytotoxicity and genotoxicity of compounds. In silico studies are added to such in vivo experiments, as they have the advantage of speed in their execution, low cost and the ability to reduce the amount of toxicity tests required. The objective of the work was to evaluate the cytotoxic, genotoxic and mutagenic potential of encapsulated and free naringenin, as well as to study the pharmacokinetic and molecular docking aspects of naringenin. Free naringenin (non encapsulated), under the conditions of established analyses, did not change the cell division index of meristematic cells from Allium cepa L. roots, and did not induce mitotic spindle changes and chromosome breaks in this test system. Based on the results of molecular anchorage studies, naringenin was anchored in the active site of the catalase enzyme (CAT), and was anchored in a distant region of the active site of the enzyme superoxide dismutase (SOD2). The results obtained in the ADMET properties studies indicated that naringenin has adequate molecular properties for bioactive substances that are orally administered, and has relatively low toxicity, factors that make naringenin a promising compound for the development of new drugs, and for a better implementation in the food industry.