Cabuk Mehmet, Gurel Ahmet, Sen Feyza, Demircan Nejat
Department of Nuclear Medicine, Faculty of Medicine, Zonguldak Karaelmas University, 67600 Kozlu, 44069 Zonguldak, Turkey.
Mol Cell Biochem. 2008 Jan;308(1-2):35-42. doi: 10.1007/s11010-007-9609-0. Epub 2007 Sep 25.
Erdosteine is a mucolytic agent having antioxidant properties through its active metabolites in acute injuries induced by pharmacological drugs. This study was designed to investigate the renoprotective potential of Erdosteine against gentamicin (GM)-induced renal dysfunction by using Technetium-99 m dimercaptosuccinic acid (Tc-99 m DMSA) uptake and scintigraphy in rats. For this purpose, male Wistar rats were randomly allotted into one of the four experimental groups: Control, Erdosteine, GM, and GM + Erdosteine groups. GM and GM + Erdosteine groups received 100 mg/kg GM intramuscularly for 6 days. In addition, Erdosteine and GM + Erdosteine groups received 50 mg/kg Erdosteine orally for 6 days. Renal function tests were assessed by serum blood urea nitrogen (BUN), creatinine levels, as well as scintigraphic and tissue radioactivity measurements with Tc-99 m DMSA. Renal oxidative damage was determined by renal malondialdehyde (MDA) levels, by antioxidant enzyme activities; superoxide dismutase (SOD) and catalase (CAT) and activities of oxidant enzymes; xanthine oxidase (XO) and myeloperoxidase (MPO). GM administration resulted in marked renal lipid peroxidation, increased XO and MPO activities and decreased antioxidant enzyme activities. GM + Erdosteine group significantly had lower MDA levels, higher SOD and CAT activities and lower XO and MPO activities, when compared to GM. Also GM + Erdosteine had lower levels of serum BUN, creatinine and higher renal tissue Tc-99 m DMSA uptake and radioactivity with respect to GM. In conclusion, our results supported a protective role of Erdosteine in nephrotoxicity associated with GM treatment.
厄多司坦是一种黏液溶解剂，通过其活性代谢产物在药物诱导的急性损伤中具有抗氧化特性。本研究旨在利用锝-99m二巯基丁二酸（Tc-99m DMSA）摄取和闪烁扫描技术，研究厄多司坦对庆大霉素（GM）诱导的大鼠肾功能障碍的肾脏保护潜力。为此，将雄性Wistar大鼠随机分为四个实验组之一：对照组、厄多司坦组、GM组和GM + 厄多司坦组。GM组和GM + 厄多司坦组肌肉注射100 mg/kg GM，持续6天。此外，厄多司坦组和GM + 厄多司坦组口服50 mg/kg厄多司坦，持续6天。通过血清血尿素氮（BUN）、肌酐水平以及用Tc-99m DMSA进行的闪烁扫描和组织放射性测量来评估肾功能。通过肾丙二醛（MDA）水平、抗氧化酶活性（超氧化物歧化酶（SOD）和过氧化氢酶（CAT））以及氧化酶活性（黄嘌呤氧化酶（XO）和髓过氧化物酶（MPO））来测定肾脏氧化损伤。给予GM导致明显的肾脏脂质过氧化、XO和MPO活性增加以及抗氧化酶活性降低。与GM组相比，GM + 厄多司坦组的MDA水平显著降低，SOD和CAT活性更高，XO和MPO活性更低。此外，与GM组相比，GM + 厄多司坦组的血清BUN、肌酐水平更低，肾组织对Tc-99m DMSA的摄取和放射性更高。总之，我们的结果支持了厄多司坦在与GM治疗相关的肾毒性中的保护作用。
