Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2–keap1 pathway

Abstract

Scope:We hypothesized that curcumin, by increasing the expression of nuclear factorerythroid-2-related factor 2 (Nrf2), could reduce oxidative stress, inflammation, and renal fibrosis in remnant kidney. Methods and results: Sprague-Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated (Nx), curcumin-treated (75 mg/kg/day, orally), and telmisartan-treated groups (10 mg/kg/day, orally; as positive control). Sham-operated rats also served as controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased creatinine clearance that were ameliorated by curcumin or telmisartan treatment. The Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch-like ECH-associated protein 1 was upregulated and heme oxygenase-1 level was significantly diminished. Consequently, Nx animals had significantly higher kidney malondialdehyde concentration and lower glutathione peroxidase activity, which was associated with the upregulation of nicotinamide adenine dinucleotide phosphatase oxidase subunit (p67 phox and p22 phox ), NF-kappaB p65, TNF-␣, TGF-␤1, cyclooxygenase-2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan.Conclusion: These findings demonstrate that, by modulating Nrf2-Keap1 pathway, the curcumin effectively attenuates oxidative stress, inflammation, and renal fibrosis, which suggest that curcumin hold promising potential for safe treatment of chronic kidney disease.

The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model

“…This result confirmed that in 5/6 nephrectomyinduced CKD, some process may halt the translocation of Nrf2 into nucleus. Similar results were found by our group 7 and Kim and Vaziri.…”

“…We have showed that curcumin, a powerful antioxidant, can attenuate oxidative stress, inflammatory response, and renal fibrosis in rats with 5/6 nephrectomy via activation of nuclear factor eryhtroid 2-related factor 2 (Nrf2). 7 Nrf2, which binded to its inhibitor Kelchlike ECH-associated protein 1 (Keap1), was a transcription factor responsible for the induction of cytoprotective and antioxidant enzymes such as heme-oxygenase-1 (HO-1) and glutathione peroxidase (GPx). 8 Therefore, compounds that act as antioxidants or induce Nrf2 may have a potential to be used as a therapy in CKD.…”

Curcumin Ameliorates Renal Fibrosis by Inhibiting Local Fibroblast Proliferation and Extracellular Matrix Deposition

“…Furthermore, curcumin at different concentrations inhibited NRK-49F stimulated by TGF-b1. Previous studies reported that curcumin exerts its antifibrotic action by a) reducing EMT (10); b) inducing apoptosis in myofibroblasts (11); c) modulating inflammatory responses (12); d) blocking NF-kB signaling, ERK signaling, and the Rac1/MLK3/JNK pathway (13 -15); e) attenuating oxidative stress (16); and f) regulating ion channels and transporters (17). However, we found out that suppression of fibroblast proliferation via activation of PPAR-g might be another antifibrotic mechanism by which curcumin functions.…”

Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

“…[18][19][20] Nrf2/Keap1 reactions could also be increased when oxidative stress occurs in the kidney. 21,22 To our knowledge, HFD increases renal inflammation by stimulating podocyte injury, which may be the key target for the treatment of CKD. 23,24 Recently, biotechnological application of nanomaterials conjugated with plant molecules has been continuously gaining importance in the therapeutic and medical field.…”