Curcumin ameliorates renal failure in 5/6 nephrectomized rats: role of inflammation

Abstract

TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.

Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in ⅚ nephrectomized rats: role of phospholipase and cyclooxygenase

“…CRF was induced in rats by the method published previously (19). Briefly, 5 ⁄6 nephrectomy of rats, weighing between 150 and 200 g, was performed using sterile techniques.…”

“…It is suggested that many of the beneficial effects of curcumin relate to its ability to suppress both acute and chronic inflammation (4). In our earlier studies, we have shown that curcumin inhibits TNF-␣-dependent NF-B activation and blocks the TNF-␣-mediated downregulation of peroxisome proliferator-activated receptor ␥ (PPAR␥) in mesangial cells (19). A similar effect of curcumin on PPAR␥ and NF-B has been shown in hepatic stellate cells, further supporting the prominent anti-inflammatory effect of curcumin (60).…”

“…Both cytokines provide a rapid form of host defense against infection; however, when present in excess, they can prove harmful (55). Proinflammatory cytokines such as TNF-␣ and IL-1␤ can act as toxins participating in uremic complications (53), generate reactive oxygen species (ROS), NF-B, and IL-6 (31,32), and attract macrophages to inflammatory sites (19). We further speculated by blocking the actions of TNF-␣ and IL-1␤ that we will be able to reduce renal dysfunction even when the therapy is started after the onset of proteinuria.…”

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

“…Moreover, this method is now being applied to the field of TCM [22][23][24][25][26] , as it could characterize the subtle metabolic interventions induced by TCM in the treatment of diseases and identify the potential implications of TCM. Therefore, in this study, an 1 H NMR-based metabolomic study was applied to investigate the extrarenal therapeutic effects of C sinensis upon 5/6 nephrectomized (5/6Nx) rats (a standard animal model with CKD [27,28] ). First, a C sinensis-dosed 5/6Nx rat group, a 5/6Nx model group and a sham-operated group were established in the study.…”

Opposite Action of Peroxisome Proliferator-activated Receptor-γ in Regulating Renal Inflammation

“…Similarly, in antiglomerular basement membrane nephritis rats, PPAR␥ agonist reduces urinary protein excretion and crescent formation and inhibits glomerular infiltration of monocytes/macrophages (15). Given that renal infiltration of inflammatory cells is an imperative pathomechanism in these disorders (16,17), it is conceivable that PPAR␥ agonists may ameliorate renal injury primarily by inhibiting inflammation rather than by regulating the insulin sensitivity or glucose metabolism. However, the molecular mechanism by which PPAR␥ activation leads to inhibition of renal inflammation remains poorly understood.…”