Renal Protective Effect of Probucol in Rats with Contrast-Induced Nephropathy and its Underlying Mechanism
Na Wang, Ri-bao Wei, Qing-ping Li, Xi Yang, Ping Li, Meng-jie Huang, Rui Wang, Guang-yan Cai, Xiang-mei Chen
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China (mainland)
Med Sci Monit 2015; 21:2886-2892
Contrast-induced nephropathy (CIN) refers to acute renal damage that occurs after the use of contrast agents. This study investigated the renal protective effect of probucol in a rat model of contrast-induced nephropathy and the mechanism of its effect.
MATERIAL AND METHODS: Twenty-eight Wistar rats were randomly divided into the control group, model group, N-acetylcysteine(NAC) group, and probucol group. We used a rat model of iopromide-induced CIN. One day prior to modeling, the rats received gavage. At 24 h after the modeling, blood biochemistry and urine protein were assessed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in renal tissue. Kidney sections were created for histopathological examination.
RESULTS: The model group of rats showed significantly elevated levels of blood creatinine, urea nitrogen, 24-h urine protein, histopathological scores, and parameters of oxidative stress (P<0.05). Both the NAC and probucol groups demonstrated significantly lower Scr, BUN, and urine protein levels compared to the model group (P<0.05), with no significant difference between these 2 groups. The NAC group and the probucol group had significantly lower MDA and higher SOD than the model group at 24 h after modeling (P<0.05). The 8-OHdG-positive tubule of the probucol group and NAC group were significantly lower than those of the model group (p=0.046, P=0.0008), with significant difference between these 2 groups (P=0.024).
CONCLUSIONS: Probucol can effectively reduce kidney damage caused by contrast agent. The underlying mechanism may be that probucol accelerates the recovery of renal function and renal pathology by reducing local renal oxidative stress.
Keywords: Animals, Acetylcysteine - chemistry, Antioxidants - chemistry, Contrast Media - adverse effects, Creatinine - blood, Deoxyguanosine - chemistry, Disease Models, Animal, Kidney - metabolism, Kidney Diseases - chemically induced, Malondialdehyde - metabolism, Nitrogen - urine, Oxidative Stress, Probucol - chemistry, Rats, Rats, Wistar, Superoxide Dismutase - chemistry