Stojiljkovic Nenad, Stoiljkovic Milan, Randjelovic Pavle, Veljkovic Slavimir, Mihailovic Dragan
Department of Physiology, University of Nis School of Medicine, Nis, Serbia.
Exp Toxicol Pathol. 2012 Jan;64(1-2):69-74. doi: 10.1016/j.etp.2010.06.008. Epub 2010 Jul 8.
Since gentamicin-induced nephrotoxicity has very important clinical consequences, different potentially therapeutic approaches to prevent or attenuate it have been proposed. Accordingly, this study aimed at determining the possible protective effects of vitamin C against gentamicin-associated acute kidney injury. Experiments were done on 40 adult Wistar rats divided into four groups of 10 animals each. G-group received gentamicin (100 mg/kg) while GVC-group received the same dose of gentamicin and vitamin C (200 mg/kg) by intraperitoneal injections on a daily basis. Animals in VC-group, serving as a positive control, received only vitamin C (200 mg/kg), and those in C-group, serving as a negative control, received saline (1 ml/day), both given intraperitoneally. All groups were treated during 8 consecutive days. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations of kidney were performed by histopathological, morphometrical and biochemical analyses in order to determine potential beneficial effects of vitamin C co-administration with gentamicin. In G-group the proximal convoluted tubules showed cytoplasm vacuolation with dark inclusions in the epithelial cells and coagulation-type necrosis, while in GVC-group necrosis was not observed. The glomerular basement membrane was significantly thickened (p<0.05) in G-group animals than in other groups. Nuclear optical density of the tubular epithelial cells in GVC-group was significantly higher (p<0.05) compared to G-group. Blood urea and serum creatinine concentration were significantly elevated, while potassium concentration was lowered in G-group compared to other groups (p<0.01 for each). Concomitant administration of gentamicin and vitamin C resulted in a significant reduction of morphological and functional kidney alterations.
由于庆大霉素诱导的肾毒性具有非常重要的临床后果，因此人们提出了不同的潜在治疗方法来预防或减轻这种毒性。相应地，本研究旨在确定维生素C对庆大霉素相关急性肾损伤的可能保护作用。实验在40只成年Wistar大鼠上进行，将其分为四组，每组10只动物。G组腹腔注射庆大霉素（100mg/kg），而GVC组每天腹腔注射相同剂量的庆大霉素和维生素C（200mg/kg）。VC组作为阳性对照，仅腹腔注射维生素C（200mg/kg），C组作为阴性对照，腹腔注射生理盐水（1ml/天）。所有组连续治疗8天。通过组织病理学、形态计量学和生化分析对庆大霉素诱导的肾脏结构改变和功能改变程度进行定量评估，以确定维生素C与庆大霉素联合使用的潜在有益效果。在G组中，近端曲管显示上皮细胞内有含深色内含物的细胞质空泡化和凝固型坏死，而在GVC组中未观察到坏死。G组动物的肾小球基底膜比其他组明显增厚（p<0.05）。与G组相比，GVC组肾小管上皮细胞的核光密度显著更高（p<0.05）。与其他组相比，G组的血尿素和血清肌酐浓度显著升高，而钾浓度降低（每项p<0.01）。庆大霉素和维生素C联合给药导致肾脏形态和功能改变显著减轻。
