Jamshidzadeh Akram, Heidari Reza, Mohammadi-Samani Soliman, Azarpira Negar, Najbi Asma, Jahani Parisa, Abdoli Narges
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmacology and Toxicology Department, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
J Biochem Mol Toxicol. 2015 Feb;29(2):57-62. doi: 10.1002/jbt.21667. Epub 2014 Oct 8.
Aminoglycoside antibiotics are widely used against Gram-negative infections. On the other hand, nephrotoxicity is a deleterious side effect associated with aminoglycoside therapy. Gentamicin is the most nephrotoxic aminoglycoside. Because of serious health complications ensue the nephrotoxicity induced by aminoglycosides, finding new therapeutic strategies against this problem has a great clinical value. This study has attempted to compare the nephrotoxic properties of gentamicin and a new nanosized formulation of this drug in a mice model. Animals were treated with gentamicin (100 mg/kg, i.p. for eight consecutive days) and nanogentamicin (100 mg/kg, i.p. for eight consecutive days). Blood urea nitrogen (BUN), plasma creatinine levels, and histopathological changes of kidney proximal tubule were monitored. It was found that gentamicin caused severe degeneration of kidney proximal tubule cells and an increase in serum creatinine and BUN. No severe injury was observed after nanogentamicin administration. This study proved that nanosized gentamicin is less nephrotoxic.
氨基糖苷类抗生素被广泛用于治疗革兰氏阴性菌感染。另一方面,肾毒性是与氨基糖苷类药物治疗相关的有害副作用。庆大霉素是肾毒性最强的氨基糖苷类药物。由于氨基糖苷类药物引起的肾毒性会导致严重的健康并发症,因此寻找针对这一问题的新治疗策略具有重要的临床价值。本研究试图在小鼠模型中比较庆大霉素和该药物的一种新型纳米制剂的肾毒性特性。动物分别接受庆大霉素(100mg/kg,腹腔注射,连续8天)和纳米庆大霉素(100mg/kg,腹腔注射,连续8天)治疗。监测血尿素氮(BUN)、血浆肌酐水平以及肾近端小管的组织病理学变化。结果发现,庆大霉素导致肾近端小管细胞严重变性,血清肌酐和BUN升高。纳米庆大霉素给药后未观察到严重损伤。本研究证明纳米庆大霉素的肾毒性较小。