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ABSTRACT INTRODUCTION: β-lapachone (β-LAP), a potent antitumor agent, has limited therapeutic use due to its low solubility and high toxicity. A possible strategy to overcome these drawbacks may be the use of adjuvants such as chitosan (CS), a cationic polysaccharide with biological properties of biocompatibility and biodegradability. OBJECTIVE: Evaluate the adjuvant action of CS as a cytoprotectant associated with β-LAP, through acute toxicity studies, evaluating histopathological changes in organs such as liver and kidneys. METHODS: The β-LAP-CS conjugate was prepared in a 1:1 ratio, administered orally, with a single dose of β-LAP of 80 mg/kg, in Swiss mice. Histomorphological and histomorphometric analyses of the kidneys and liver were performed. RESULTS: In the histomorphological studies of the tested groups, we observed that the hepatocytes of animals treated with the free drug presented morphological alterations, such as cytoplasmic vacuolization, cellular extravasation, atypical and pyknotic nuclei. In this same group, the kidneys presented granular aspects suggestive of glomerulonephritis. These changes were not found in the control group and in animals treated with CS-conjugated β-LAP. There was no statistical difference in the histomorphometric analyses of the distal tubules and the renal glomeruli between the three groups analyzed, even with evident histomorphological alterations. After histomorphometric studies, it was observed that the area of hepatocytes and their cell nuclei presented a statistically significant difference between the animals treated with free β-LAP and the β-LAP-CS. CONCLUSION: The decrease in β-LAP toxicity after conjugation may be related to the hepatoprotective property of CS.
RESUMO INTRODUÇÃO: A β-lapachona (β-LAP), um potente agente antitumoral, tem uso terapêutico limitado devido a sua baixa solubilidade e elevada toxicidade. Uma possível estratégia para contornar esses inconvenientes pode ser a utilização de adjuvantes como a quitosana (QS), um polissacarídeo catiônico com propriedades biológicas, como biocompatibilidade e biodegradabilidade. OBJETIVO: Avaliar a ação adjuvante da QS como citoprotetor associada à β-LAP por meio de estudos de toxicidade aguda, verificando as alterações histopatológicas em órgãos como fígado e rins. MÉTODOS: Um conjugado da β-LAP-QS foi preparado na proporção 1:1, administrado por via oral, com dose única da β-LAP de 80 mg/kg, em camundongos Swiss. Foram realizadas análises histomorfológicas e histomorfométricas dos rins e do fígado desses animais. RESULTADOS: Nos estudos histomorfológicos dos grupos testados, observamos que os hepatócitos dos animais tratados com a droga livre apresentaram alterações morfológicas, como vacuolização do citoplasma, extravasamento celular, núcleos atípicos e picnóticos. Nesse mesmo grupo, os rins apresentaram aspectos granulosos sugestivos de glomerulonefrite. Essas alterações não foram encontradas no grupo-controle e nos animais tratados com a β-LAP conjugada com QS. Não houve diferença estatística nas análises histomorfométricas dos túbulos distais e dos glomérulos renais entre os três grupos analisados, mesmo com alterações histomorfológicas evidentes. Após estudos histomorfométricos, foi observado que a área dos hepatócitos e seus núcleos celulares apresentaram diferença estatística significativa entre os animais tratados com a β-LAP livre e o conjugado β-LAP-QS. CONCLUSÃO: A diminuição da toxicidade da β-LAP, após ser conjugada, pode estar relacionada com a propriedade hepatoprotetora da QS.
RESUMO
This research evaluated the importance of the adsorption properties of chitosan a chitosan/zeolite conjugate film for the removal of Cr(VI) ions from solutions in the 5-260 mg/L concentration range, when the pH was adjusted to 4.0 and 6.0. The uptake capacities of the films formed by chitosan and by the chitosan/zeolite conjugate were calculated by mass balance. The equilibrium isotherms were fitted to the Langmuir, Freundlich and Redlich-Peterson models. The chitosan film seems to be a good sorbent for Cr(VI) at pH 4, but its physical instability suggests the need for a more resilient support. Due to this fact zeolite was added to the chitosan matrix in solution and a chitosan/zeolite (CS/Zeo) film was thus formed. The solubility of the film and the characterization of the different matrices by FTIR, TGA and X-Ray showed that a cross-linked structure was formed between the chitosan and zeolite and the solubility of the film increased. In this study, the low manufacturing cost of the CS/Zeo matrix, the good uptake of Cr(VI) at acidic pH (17.28 mg/g) and the non desorption of Cr(VI) from the film in water suggests this combination should be tested in industrial environment.
