Rocha, Hugo Alexandre de OliveiraAquino, Leonardo de Medeiros2025-08-202025-08-202025-05-26AQUINO, Leonardo de Medeiros. Previsão do efeito terapêutico e avaliação de riscos de carotenóides e retinóides em um modelo de urolitíase por meio de análise in silico e ensaios in vitro. Orientador: Dr. Hugo Alexandre de Oliveira Rocha. 2025. 81f. Dissertação (Mestrado em Bioquímica e Biologia Molecular) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2025.https://repositorio.ufrn.br/handle/123456789/65247Oxidative stress can cause several damages to the organism and its molecules. An example of the consequences of this stress is urolithiasis, the formation of renal calculi, contributing to the formation of crystals, mainly calcium oxalate crystals, monohydrate (COM) and dihydrate (COD). Beta-carotene (BCAR), astaxanthin (AST) and retinol (RET) are described as antioxidant molecules that can be used to combat the damage caused by oxidative stress. However, there is no data regarding how these three molecules are used to prevent or specifically combat urolithiasis. In this context, this study initially evaluated in vitro the potential of BCAR, AST and RET, known antioxidants, as inhibitors of renal calculi formation. BCAR, AST or RET (10 and 15 µg/mL) were not toxic to canine renal cell line (MDCK) cells, but they were also unable to protect these cells from damage caused by the presence of H2O2. Regarding the direct formation of calcium oxalate crystals, it was found that the compounds evaluated here equally affected the balance between the quantity of the types of calcium oxalate crystals formed, inducing the formation of a greater quantity of COD crystals, which are more harmful. These data, although initial, demonstrate an undesirable effect not yet described for this class of molecules. Given this new context, in-silico techniques were used to evaluate carotenes (BCAR and lycopene), retinoids (RET and isotretinoin) and xanthophylls (AST, fucoxanthin, zeaxanthin, betacryptoxanthin, canthaxanthin and lutein) and identify other possible adverse effects. Within their relevant groups, similarities can be seen in the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profile of the compounds evaluated. Using the PredHerg platform, we found weak cardiotoxic potential for lycopene, beta-cryptoxanthin, and fucoxanthin, and moderate cardiotoxic potential for lutein. Using the PredSkin platform, we found that lycopene and the tested xanthophylls, except canthaxanthin, have the potential to cause allergic skin reactions. The results of this study suggest that although BCAR, AST, and RET are known antioxidants, they may have undesirable negative effects on kidney stone formation by promoting the formation of more harmful calcium oxalate crystals. Furthermore, a symbiotic analysis revealed potential risks of cardiotoxicity and allergic skin reactions for some of the compounds evaluated. These initial results highlight the need for further investigation into the safety and efficacy of these antioxidant molecules, especially in the context of kidney health and oxidative stress.pt-BRAcesso AbertoAntioxidantesEstresse oxidativoADMETSwiss target predictionmasterThesisCIENCIAS BIOLOGICAS