a Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine , Istanbul Medipol University , Istanbul , Turkey.
b Department of Physiology, International School of Medicine , Istanbul Medipol University , Istanbul , Turkey.
Ren Fail. 2018 Nov;40(1):423-434. doi: 10.1080/0886022X.2018.1489286.
To investigate the molecular mechanisms of colistimethate sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) against nephrotoxicity.
Twenty-eight Wistar rats were divided into four groups comprised of control, colistin, NAC, and colistin-NAC co-treatment, respectively. Serum creatinine and urine N-acetyl-β-d-glucosaminidase (NAG) levels were measured at different time intervals. Histological changes, apoptosis, total oxidant and antioxidant status, and the expression levels of endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue.
In the colistin group, post-treatment creatinine levels were higher than pretreatment levels (p = .001). There was a significant increase in urine NAG level following colistin treatment on day 10, compared to the baseline value and the first day of treatment (p = .001 and .0001, respectively). Urine NAG levels were higher in the colistin group on the 10th day of treatment than in the other groups (p < .01). Colistin treatment increased the apoptosis index and renal histological damage score (RHDS) significantly and these changes were reversed in NAC co-treatment (RHSD and apoptosis index were 45 and 0 for sterile saline group, 29 and 2 for NAC group, 122 and 7 for colistin group, and 66 and 2 for colistin + NAC group). We observed no difference between groups regarding total antioxidant and total oxidant status in the kidneys. The expression levels of eNOS, SOD2, and MMP3 decreased significantly in the kidneys of colistin-treated rats; these changes were reversed in the kidneys of NAC co-treated rats.
N-acetylcysteine prevented colistin-induced nephrotoxicity through activation of expression levels of SOD2, eNOS, and MMP3.
研究黏菌素联合应用 N-乙酰半胱氨酸（NAC）对肾毒性的分子机制及保护作用。
将 28 只 Wistar 大鼠随机分为 4 组，分别为对照组、黏菌素组、NAC 组和黏菌素联合 NAC 组。分别于不同时间点检测血清肌酐和尿 N-乙酰-β-D-氨基葡萄糖苷酶（NAG）水平。检测肾组织的形态学变化、细胞凋亡、总氧化还原状态及内皮型一氧化氮合酶（eNOS）、超氧化物歧化酶 2（SOD2）和基质金属蛋白酶 3（MMP3）的表达水平。
黏菌素组治疗后血肌酐水平高于治疗前（p=0.001）。黏菌素治疗第 10 天，尿 NAG 水平较基线值和治疗第 1 天明显升高（p=0.001 和.0001），且高于其他组（p<.01）。黏菌素治疗组的细胞凋亡指数和肾组织损伤评分（RHDS）明显升高，NAC 联合治疗可逆转这些变化（RHDS 和凋亡指数分别为无菌生理盐水组 45 和 0、NAC 组 29 和 2、黏菌素组 122 和 7、黏菌素联合 NAC 组 66 和 2）。各组间肾脏总抗氧化和总氧化状态无差异。黏菌素治疗组大鼠肾脏中 eNOS、SOD2 和 MMP3 的表达水平明显降低，NAC 联合治疗组大鼠肾脏中的这些变化得到逆转。
NAC 通过激活 SOD2、eNOS 和 MMP3 的表达水平，预防黏菌素引起的肾毒性。
