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

Abstract

Ghosh SS, Krieg R, Massey HD, Sica DA, Fakhry I, Ghosh S, Gehr TW. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in 5 ⁄6 nephrectomized rats: role of phospholipase and cyclooxygenase. Am J Physiol Renal Physiol 302: F439-F454, 2012. First published October 26, 2011 doi:10.1152/ajprenal.00356.2010.-Previously, we showed that curcumin prevents chronic kidney disease (CKD) development in 5 ⁄6 nephrectomized (Nx) rats when given within 1 wk after Nx (Ghosh SS, Massey HD, Krieg R, Fazelbhoy ZA, Ghosh S, Sica DA, Fakhry I, Gehr TW. Am J Physiol Renal Physiol 296: F1146 -F1157, 2009). To better mimic the scenario for renal disease in humans, we began curcumin and enalapril therapy when proteinuria was already established. We hypothesized that curcumin, by blocking the inflammatory mediators TNF-␣ and IL-1␤, could also reduce cyclooxygenase (COX) and phospholipase expression in the kidney. Nx animals were divided into untreated Nx, curcumin-treated, and enalapril-treated groups. Curcumin (75 mg/kg) and enalapril (10 mg/kg) were administered for 10 wk. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was comparably reduced by curcumin and enalapril, with only enalapril significantly lowering blood pressure. Compared with controls, Nx animals had higher plasma/kidney TNF-␣ and IL-1␤, which were reduced by curcumin and enalapril treatment. Nx animals had significantly elevated kidney levels of cytosolic PLA 2, calcium-independent intracellular PLA 2, COX 1, and COX 2, which were comparably reduced by curcumin and enalapril. Studies in mesangial cells and macrophages were carried out to establish that the in vivo increase in PLA 2 and COX were mediated by TNF-␣ and IL-1␤ and that curcumin, by antagonizing the cytokines, could significantly reduce both PLA2 and COX. We conclude that curcumin ameliorates CKD by blocking inflammatory signals even if it is given at a later stage of the disease.

Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR−/− Mice – Role of Intestinal Permeability and Macrophage Activation

“…Restoration of Western diet-induced decrease in IAP activity by selective gut decontamination as well as with curcumin supplementation shown here strongly suggests a potential therapeutic use of this strategy for multiple diseases. In this regard, it is noteworthy that we have earlier demonstrated significant improvement in chronic kidney disease by curcumin supplementation [28], [29]. The two interventions examined in this study also decreased para-cellular transport and prevented western diet-induced reduction in the expression of tight junction proteins (ZO-1 and Claudin-1).…”

Cardiac Myocyte-Derived Follistatin-Like 1 Prevents Renal Injury in a Subtotal Nephrectomy Model

“…36,37 In this regard, antiinflammatory agents have been reported to attenuate the progression of kidney damage. [38][39][40] Our study with loss-of-function genetic manipulations indicates that reduced levels of circulating Fstl1 exacerbate renal injury after subtotal nephrectomy, with an accompanying upregulation of proinflammatory cytokines and NADPH oxidase components that are the major source of reactive oxygen species. Conversely, systemic delivery of Fstl1 using adenovirus-mediated gene transfer led to downregulation of proinflammatory mediators in the remnant kidney.…”

Colchicine attenuates renal injury in a model of hypertensive chronic kidney disease

“…Indeed, colchicine is best known for its use as an anti-inflammatory agent, effective in the treatment of the inflammatory response of numerous conditions including gout, familial Mediterranean fever, and Behcet's disease. A role for immune cell infiltration, including that of monocytes/macrophages and T-cells, has been shown in mediating hypertensive renal damage through their release of cytokines such as TNF-␣, IL-1, and TGF-␤ (12,18). Agents that modulate the inflammatory response such as mycophenolate mofetil (MMF) and the leukocyte migration inhibitor FTY720 were shown to decrease not only renal infiltration by inflammatory cells, but also proteinuria and fibrosis (18,35).…”

“…Renal inflammatory cell infiltration has been shown to contribute to injury in the remnant model (12,18,32). Colchicine is well-known as an anti-inflammatory agent, affecting the mobility and function of cells (21,38).…”