SCOPE: Acute kidney injury (AKI) is the most frequent and serious complication in sepsis, a potentially deadly inflammatory response induced by bacterial, viral, or fungal infection. LPS-induced AKI is associated with an abnormal inflammatory response, including renal endothelial dysfunction and renal inflammation. Resveratrol, a natural phytoalexin with low toxicity and anti-inflammatory properties, is known to protect endothelial cells and modulate the immune response in sepsis. METHODS AND RESULTS: This study investigates the potential protective effects of resveratrol on AKI induced by LPS exposure of mice. Resveratrol was administered as a pre- and posttreatment, or as a posttreatment alone following LPS injection and compared to control groups. Resveratrol significantly improved kidney function and lowered serum and kidney tissue inflammatory cytokine levels. Consistently, resveratrol prevented endotoxin-induced disruption of endothelial cell permeability and inhibited inflammation of kidney tissue. Resveratrol treatment attenuated the effects of LPS on macrophages, with significant inhibition of activation, cytokine release, and Toll-like receptor 4 activation. Resveratrol treatment also resulted in decreased expression of iNOS, Bcl-2, and Bcl-xL in macrophages, which was linked with induction of apoptosis in macrophages. CONCLUSION: Our studies suggest that resveratrol might represent a novel therapeutic agent to prevent and treat sepsis-induced AKI.
SCOPE: Acute kidney injury (AKI) is the most frequent and serious complication in sepsis, a potentially deadly inflammatory response induced by bacterial, viral, or fungal infection. LPS-induced AKI is associated with an abnormal inflammatory response, including renal endothelial dysfunction and renal inflammation. Resveratrol, a natural phytoalexin with low toxicity and anti-inflammatory properties, is known to protect endothelial cells and modulate the immune response in sepsis. METHODS AND RESULTS: This study investigates the potential protective effects of resveratrol on AKI induced by LPS exposure of mice. Resveratrol was administered as a pre- and posttreatment, or as a posttreatment alone following LPS injection and compared to control groups. Resveratrol significantly improved kidney function and lowered serum and kidney tissue inflammatory cytokine levels. Consistently, resveratrol prevented endotoxin-induced disruption of endothelial cell permeability and inhibited inflammation of kidney tissue. Resveratrol treatment attenuated the effects of LPS on macrophages, with significant inhibition of activation, cytokine release, and Toll-like receptor 4 activation. Resveratrol treatment also resulted in decreased expression of iNOS, Bcl-2, and Bcl-xL in macrophages, which was linked with induction of apoptosis in macrophages. CONCLUSION: Our studies suggest that resveratrol might represent a novel therapeutic agent to prevent and treat sepsis-induced AKI.
Authors: Peter J Nelson; Andrew J Rees; Matthew D Griffin; Jeremy Hughes; Christian Kurts; Jeremy Duffield Journal: J Am Soc Nephrol Date: 2011-12-01 Impact factor: 10.121
Authors: H Bryant Nguyen; Stephen W Corbett; Kevin Menes; Thomas Cho; Jennifer Daugharthy; Walter Klein; William A Wittlake Journal: Acad Emerg Med Date: 2005-12-19 Impact factor: 3.451
Authors: H D Flad; E Grage-Griebenow; F Petersen; B Scheuerer; E Brandt; J Baran; J Pryjma; M Ernst Journal: Pathobiology Date: 1999 Impact factor: 4.342
Authors: Chang Xu; Anthony Chang; Bradley K Hack; Michael T Eadon; Seth L Alper; Patrick N Cunningham Journal: Kidney Int Date: 2013-07-31 Impact factor: 10.612