Optimized Chitosan-Coated Gliadin Nanoparticles Improved the Hesperidin Cytotoxicity over Tumor Cells

Abstract Hesperidin is a natural compound which is found in citric fruits and presents antitumor and antimicrobial activities. However, the in vivo efficacy of Hesperidin is reduced due to its low oral bioavailability. Protein-based nanoparticles have been applied to improve biological parameters of drugs and natural compounds. Gliadin is a monomeric protein present in wheat. In this study, gliadin-based nanoparticles containing hesperidin were obtained by desolvation technique and a Taguchi orthogonal array design was employed to optimize the formulation. The independent variables were set as concentration of CaCl2 (0.5; 1 or 2%) and stabilizing agent (Pluronic F68, Tween 80 or sodium caseinate). The dependent variables consisted of mean diameter, polydispersity index, zeta potential, and encapsulation efficiency. The results showed significant effects on the dependent variables when 1% CaCl2 and Pluronic F68 were used. The optimized formulation was coated with chitosan to increase the physical stability of the nanoparticles. The final nanoparticles presented a mean diameter of 321 nm and polydispersity index of 0.217, and spherical shape. After coating, the Zeta potential was +21 mV, and the encapsulation efficiency was 73 %. The in vitro release assay showed that about 98% of the drug was released from the nanoparticles after 48 h. Moreover, the nanoparticles reduced hesperidin cytotoxicity on healthy cells (Vero cells) and improved the cytotoxicity on tumor cells (HeLa, PC-3 and Caco-2 cells). Results showed that the chitosan-coated gliadin nanoparticles are potential carriers for hesperidin delivery for cancer treatment.

Sepsis-induced acute kidney injury: kidney protection effects by antioxidants / Lesión renal aguda inducida por sepsis: efecto de protección renal de los antioxidantes / Lesão renal aguda induzida pela sepse: efeito de proteção renal dos antioxidantes

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

RESUMEN Objetivo: Evaluar la acción antioxidante de agentes como la N-acetilcisteína y Diosmina-Hesperidina en modelo experimental de lesión renal aguda inducida por sepsis en ratones. Método: Fueron utilizados veinte ratones Wistar, adultos y machos, divididos en los grupos: Control (laparotomía sin inducción de sepsis abdominal), Sepsis (modelo experimental de sepsis con ligadura y punción de ciego-LPC), N-acelsisteína+Sepsis y Diosmina Hesperidina+Sepsis. Se evaluaron parámetros fisiológicos (temperatura, glucemia y presión arterial promedio), la función renal (clearance de creatinina), el estrés oxidativo (peróxidos urinarios) e histología renal. Resultados: Los animales sometidos a LPC (sepsis) presentaron reducción de la temperatura corporal, de la presión arterial promedio, del clearance de creatinina e incremento de niveles de peróxidos de hidrógeno urinarios. El tratamiento con Diosmina-Hesperidina mejoró la función renal, reduciendo la excreción de metabolitos oxidativos. Conclusión: Este estudio destacó la acción renoprotectora antioxidante de la Diosmina-Hesperidina en el modelo experimental de lesión renal aguda inducida por sepsis.

RESUMO Objetivo: Avaliar a ação antioxidante de agentes como a N-acetilcisteína e diosmina-hesperidina em modelo experimental de lesão renal aguda induzida pela sepse em ratos. Método: Foram utilizados vinte ratos Wistar, adultos e machos, divididos nos seguintes grupos: Controle (laparotomia sem indução de sepse abdominal), Sepse (modelo experimental de sepse com ligadura e punção do cécum- LPC), N-acetilcisteína+Sepse e Diosmina Hesperidina+Sepse. Foram avaliados parâmetros fisiológicos (temperatura, glicemia e pressão arterial média), função renal (clearance de creatinina), estresse oxidativo (peróxidos urinários) e histologia renal. Resultados: Os animais submetidos à LPC (sepse) apresentaram redução da temperatura corporal, da pressão arterial média, do clearance de creatinina e elevação nos níveis de peróxidos de hidrogênio urinários. O tratamento com a Diosmina-Hesperidina melhorou a função renal com redução na excreção dos metabólitos oxidativos. Conclusão: Este estudo destacou a ação renoprotetora antioxidante da Diosmina-Hesperidina no modelo experimental de lesão renal aguda induzida pela sepse.

Protective effect of hesperidin on nicotine induced toxicity in rats.

Nicotine administration (2.5 mg/kg of body weight, sc, 5 days a week for 22 weeks) enhanced lipid peroxidative indices (thiobarbituric acid reactive substances and hydroperoxides) accompanied by a significant increase in the marker enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase and lactate dehydrogenase and elevated levels of cholesterol, triglycerides, phospholipids and free fatty acids in Wistar rats. There was a significant protection by hesperidin administration at different doses (25, 50, 75, 100 and 150 mg/kg body weight) in nicotine-treated rats. However, the effect of hesperidin was more significant at 25mg/kg dose. The results suggest that hesperidin exerts the protective effects by modulating the extent of lipid peroxidation. The results are supported by histopathological observations of lung, liver and kidney.