Curcumin ameliorates macrophage infiltration by inhibiting NF-κB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy

Abstract

BackgroundChronic inflammation plays an important role in the progression of diabetic nephropathy (DN) and that the infiltration of macrophages in glomerulus has been implicated in the development of glomerular injury. We hypothesized that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory effect, would ameliorate macrophage infiltration in streptozotocin (STZ)-induced diabetic rats.MethodsDiabetes was induced with STZ (55 mg/kg) by intraperitoneal injection in rats. Three weeks after STZ injection, rats were divided into three groups, namely, control, diabetic, and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 weeks. The rats were sacrificed 11 weeks after induction of diabetes. The excised kidney was used to assess macrophage infiltration and expression of various inflammatory markers.ResultsAt 11 weeks after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, blood urea nitrogen and proteinuria, along with marked reduction in the body weight. All of these abnormalities were significantly reversed by curcumin. Hyperglycemia induced the degradation of IκBα and NF-κB activation and as a result increased infiltration of macrophages (52%) as well as increased proinflammatory cytokines: TNF-α and IL-1β. Curcumin treatment significantly reduced macrophage infiltration in the kidneys of diabetic rats, suppressed the expression of above proinflammatory cytokines and degradation of IκBα. In addition, curcumin treatment also markedly decreased ICAM-1, MCP-1 and TGF-β1 protein expression. Moreover, at nuclear level curcumin inhibited the NF-κB activity.ConclusionOur results suggested that curcumin treatment protect against the development of DN in rats by reducing macrophage infiltration through the inhibition of NF-κB activation in STZ-induced diabetic rats.

Diabetes-Induced Renal Injury in Rats Is Attenuated by Suramin

“…Activation of renal endothelial cell ICAM-1 and the contributions of leukocytes in the pathophysiology of renal inflammation in DN have been documented previously (Fornoni et al, 2008;Soetikno et al, 2011;Tang et al, 2011). We found that ICAM-1 expression increased 2.5-fold in STZ rats and that suramin completely blocked the increased ICAM-1 expression in STZ rat kidneys (Fig.…”

“…Circulating leukocytes use endothelial cell transmembrane ICAM-1 as an anchor to transmigrate and cause inflammation (Nayak, 2005). Activation of renal endothelial cell ICAM-1 expression by hyperglycemia along with subsequent leukocyte infiltration has been suggested to be an important event in the pathophysiology of tubular inflammation in DN (Fornoni et al, 2008;Soetikno et al, 2011;Wu et al, 2011;Lin et al, 2012). We observed that suramin intervention after induction of diabetes decreased phosphorylation of p65, blocked ICAM-1 expression, and decreased leukocyte infiltration.…”

“…It has been well documented that activation of NF-B is a major contributor in inflammation associated with DN (Fornoni et al, 2008;Soetikno et al, 2011). Hyperglycemia is also known to induce activation of mitogen-activated protein kinases (e.g., ERK1/2), the STAT-3 pathway, and/or G proteinmediated aberrant expression of ECM proteins (Marrero et al, 2006;Catania et al, 2007;Tan et al, 2007).…”

Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales

“…Specific examples include diabetic cardiomyopathy (Westermann et al, 2007) and diabetic nephropathy (Mensah-Brown et al, 2005;Navarro et al, 2005). In the latter, successful experimental treatments include combined insulin (overcoming insulin resistance) and curcumin [reducing the inflammatory response (Sharma et al, 2007)] as well as curcumin alone (Soetikno et al, 2011). A commercial anti-TNF biological agent has also been used, to good effect, for this purpose (Yamakawa et al, 2011).…”

Role of Curcumin as Anti-Oxidant in Nephrotoxicity

“…Also according to some other studies, it was suggested that, the nephroprotective effect of curcumin was related to the downregulation of the profibrotic cytokines vascular endothelial growth factor (VEGF), TGF-ß, CTGF and osteopontin as in extracellular matrix proteins fibronectin and collagen IV [20]. Cellular signalings such as inhibition of nuclear factor kappa-lightchain enhancer of activated B cells (NF-κB) [26,27] and decrease of macrophage infiltration [27] histone acetyltransferase p300 protein and oxidative stress [26] also these mechanisms may be as those, through which the curcumin protects against diabetic nephropathy. Also, Waseem M et al [28] at 2013 in a research has shown that curcumin could have protective effect in acute nephrotoxicity model induced with cisplatin in rat and reduced lipid peroxidation and protein carbonyl levels [28].…”