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

Abstract

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.

Role of Autophagy on Heavy Metal-Induced Renal Damage and the Protective Effects of Curcumin in Autophagy and Kidney Preservation

“…A study in human kidney tubular epithelial cells (HKCs) found that curcumin exposure avoided the epithelial-to-mesenchymal transition through Akt/mTOR/p70S6K pathway inhibition [28]. In the same way, in the 5/6 nephrectomy-induced chronic kidney damage model, curcumin decreased the phosphorylation of mTOR and its targets (p70S6K and 4E-BP1) [73]. Although in both cases the study of autophagy was not the aim, the possible participation of this may be considered, since the Akt/mTOR pathway modulation is considered a classic mechanism for the regulation of autophagy [74,75].…”

Curcumin relieves arecoline‐induced oral submucous fibrosis via inhibiting the LTBP2/NF‐κB axis

“…Besides, curcumin improved renal fibrosis in rats by inactivating the mTOR/HIF-1α/VEGF signaling pathway (He et al, 2019). Curcumin also affected glycolysis of pancreatic cancer by inhibiting HIF-1α (Guo et al, 2022).…”

“…Wang et al reported that Curcumin inactivated HIF‐1α in a PGC‐1α/SirT3‐dependent manner, thereby promoting skin wound healing (Wang, Shen, et al, 2020). Besides, curcumin improved renal fibrosis in rats by inactivating the mTOR/HIF‐1α/VEGF signaling pathway (He et al, 2019). Curcumin also affected glycolysis of pancreatic cancer by inhibiting HIF‐1α (Guo et al, 2022).…”

Association of Nuclear Receptor Coactivators with Hypoxia-Inducible Factor-1α in the Serum of Patients with Chronic Kidney Disease

“…However, currently, the effects of HIF and vascular endothelial growth factor (VEGF) are not well known. Some studies on renal diseases found that HIF-1 α played a protective role [ 13 – 15 ], but others reported that it was a risk factor [ 16 – 18 ]. Current evidence indicated that HIF-1 α could be regulated by some NR [ 19 – 21 ]; however, there was no report showing the relationship between NCOAs and HIF-1 α .…”