Probucol Protects Against Contrast-Induced Acute Kidney Injury via the Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2)/JNK-Caspase 3 Pathway in Diabetic Rats

• Published in: Medical science monitor 2019-02, Vol.25, p.1038-1045
• Main Authors: Ma, Xingxing, Jiao, Zhanquan, Liu, Yanhong, Chen, Jun, Li, Guangping, Liu, Tong, Tse, Gary, Yuan, Ruyu
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - prevention & control; Animals; Antioxidants - pharmacology; Apoptosis - drug effects; Caspase 3 - drug effects; Caspase 3 - metabolism; Contrast Media - adverse effects; Contrast Media - pharmacology; Diabetes Mellitus, Experimental; Diabetic Nephropathies - metabolism; Kidney - pathology; Kidney Tubules - pathology; Lab/In Vitro Research; Male; MAP Kinase Signaling System - drug effects; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Oxidative Stress - drug effects; Probucol - pharmacology; Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 1643-3750; 1234-1010; 1643-3750
• DOI: 10.12659/MSM.913106

BACKGROUND Contrast-induced acute kidney injury is an important clinical problem, yet its pathogenic mechanisms are incompletely understood. In this study we explored the potential beneficial effects of probucol as treatment of contrast-induced acute kidney injury in diabetic rats. MATERIAL AND METHODS Rats were divided into 3 groups: i) diabetic control, ii) diabetic with contrast, and iii) probucol treatment groups. Probucol was administered by gavage and the contrast diatrizoate (60%) was injected via femoral vein. After 24 h, the rats were sacrificed and samples were taken to measure biochemical indicators. Pathological damage of renal tubules was evaluated by HE staining. Expression of Bcl-2, Bax, p-ERKs, and p-JNK proteins in the kidneys was examined by Western blotting, whereas expression level of caspase-3 in kidneys was detected by immunohistochemistry. RESULTS Compared to the probucol treatment group, the diabetes with contrast group showed higher serum creatinine and lower creatinine clearance. The pathological changes of kidneys in the probucol treatment group were improved compared with the contrast group. Moreover, Western blot analyses revealed that use of contrast agent led to lower p-ERK1/2, higher p-JNK, lower Bcl-2, and higher Bax levels, which were reversed by probucol. Finally, immunohistochemical findings revealed higher caspase-3 after contrast use, which was partially reversed by probucol. CONCLUSIONS Probucol exerts protective effects on contrast-induced acute kidney injury in diabetic rats by inhibition of renal cell apoptosis. This is achieved by reducing mitochondrial caspase-3 expression through increasing and decreasing the expression of the upstream mediators p-ERK1/2 and p-JNK, respectively.