Instituto de Investigación en Enfermedades Crónico-Degenerativas, Centro de Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Jalisco, Mexico.
Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Jalisco, Mexico.
Int J Mol Sci. 2022 May 12;23(10):5392. doi: 10.3390/ijms23105392.
Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-β/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.
肾纤维化是慢性肾损伤的终末阶段，其特征为肾小球硬化和小管间质纤维化伴实质破坏。槲皮素属于研究最多的类黄酮之一，具有抗氧化、抗炎、抗纤维化和抗肿瘤活性。它可调节 TGF-β/Smad 信号通路，减少促纤维化表达分子，并诱导抗氧化、抗炎和抗纤维化分子的表达。然而，槲皮素的水溶性差，吸收和生物利用度低。通过开发纳米粒制剂可以改善几种生物活性化合物的溶解度和生物利用度，从而解决了这一限制。因此，我们旨在研究槲皮素纳米粒制剂的体内抗纤维化作用。雄性 C57BL/6 小鼠用 50mg/kg 的腺嘌呤诱导慢性肾衰竭 4 周。动物随机分组，用 25、50 或 100mg/kg 的槲皮素，大颗粒或纳米粒制剂进行治疗。我们进行了生化、组织学和分子分析，以评估和比较大颗粒与纳米粒制剂对肾脏损伤的影响。结果表明，较小剂量的纳米粒制剂在预防肾脏损伤方面与较大剂量的大颗粒制剂具有相同的有益作用。这一发现意味着达到所需治疗效果所需的槲皮素消耗量减少。
