Evaluation of Two Biomarkers as Early Indicators for Assessment of Gentamycin-induced Nephrotoxicity in Vivo and in Vitro
The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine.Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity.Early detection of renal damage is critical in preclinical drug development.This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil getatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity.In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI).Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro.Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose-and time-dependent increase in the expression of KIM-1 and NGAL.The expressions of the two biomarkers changed prior to proximal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo.In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection ofnephrotoxic effects in vitro.
Gentamycin nephrotoxicity KIM-1 NGAL HK-2 cells
Chen Meng-Lu Fang Jing Tang Li Geng Yi Luo Qi-Hui Sun Feng-Jiao Chen Zheng-li Li Ming-yang Zeng Wen Gong Li Cheng An-chun Peng Xi
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicin Sichuan Industrial Institute of Antibiotics in China National Pharmaceutical Group, Chengdu, Sichuan Sichuan Primed Biological Technology Co., Ltd/National Experimental Macaque Reproduce Laboratory, Ya
国内会议
南京
英文
51-59
2014-09-19（万方平台首次上网日期，不代表论文的发表时间）