Curcumin Ameliorates Chronic Renal Failure in 5/6 Nephrectomized Rats by Regulation of the mTOR/HIF-1α/VEGF Signaling Pathway

• Published in: Biological & pharmaceutical bulletin Vol. 42; no. 6; pp. 886 - 891
• Main Authors: He, Yangbiao, Lang, Xujun, Cheng, Dong, Yang, Zhihao
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-06-2019; Japan Science and Technology Agency
• Subjects: Activation; Animals; Blood; Change detection; chronic renal failure; Curcumin; Curcumin - pharmacology; Everolimus - pharmacology; Fibrosis; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; hypoxia-inducible factor-1α; Hypoxia-inducible factors; Intracellular Signaling Peptides and Proteins - metabolism; Kidney Failure, Chronic - drug therapy; Kidney Failure, Chronic - metabolism; Kidneys; Male; mammalian target of rapamycin; Models, Animal; Nephrectomy; Proteinuria; Rapamycin; Rats; Rats, Sprague-Dawley; Renal failure; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Rodents; Signal transduction; Signal Transduction - drug effects; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; TOR Serine-Threonine Kinases - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - metabolism; Western blotting; mammalian target of rapamycin; hypoxia-inducible factor-1α; chronic renal failure; vascular endothelial growth factor
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00787

Previous studies implicated the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway in renal fibrosis and found that curcumin could suppress the expression of mTOR. Therefore, the aim of the present study was to investigate the therapeutic effects of curcumin against chronic renal failure (CRF) in a rat model induced by 5/6 nephrectomy through inhibition of mTOR/HIF-1α/VEGF signaling. A total of 70 male Sprague–Dawley rats were divided into seven groups: a sham group, a CRF group, and five treatment groups. Except for the sham rats, all rats underwent 5/6 nephrectomy to induce CRF. The 5/6 nephrectomized rats received treatment with curcumin vehicle, everolimus vehicle, curcumin, everolimus, or the combination of curcumin and everolimus. Everolimus, a specific inhibitor of mTOR, was used as a positive control. At the end of treatment, blood biochemical indexes, proteinuria and the kidney index were detected. Moreover, histological change was examined by hematoxylin and eosin staining, and protein expression levels were detected by Western blotting. The blood biochemical indexes, proteinuria, and kidney index were increased in the CRF group as compared to the sham group, which was accompanied by marked activation of the mTOR/HIF-1α/VEGF pathway. However, curcumin, as well as everolimus, restored or ameliorated these changes. These results indicate that activation of the mTOR/HIF-1α/VEGF signaling pathway plays an important role in the occurrence and development of CRF, and that curcumin has renoprotective effects by blocking activation of this pathway.