Simvastatin Inhibits Inflammation in Ischemia-Reperfusion Injury

Abstract

Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue injury. The aim of this research was to investigate the protective effect of simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected to hind limb ischemic insult for 2 h and were simultaneously administered an intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and P-selectin, were assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and adhesion in vitro was assessed to indicate leukocyte recruitment at the site of inflammation. Quantitative measurement of skeletal muscle tissue injury was performed. The fluorescent dye level in tissue and serum was used to determine hind limb vascular leakage and tissue edema after I/R. Systemic and differentiated leukocytes were also counted. Simvastatin significantly reduced MIP-2, KC, TNF-α, MPO, IL-6, and P-selectin levels compared to the sham group and I/R plus pretreatment with phosphate-buffered saline (PBS) group (P<0.05). Compared to the sham group and I/R plus PBS group, the I/R plus simvastatin group had attenuated inflammation, vascular leakage, and muscular damage (P<0.05). Simvastatin also significantly inhibited leukocyte rolling and adhesion compared to PBS (P<0.05). Our results suggest that simvastatin may be an effective protectant against tissue injury associated with I/R.

Schisandrin B Prevents Hind Limb from Ischemia-Reperfusion-Induced Oxidative Stress and Inflammation via MAPK/NF-κB Pathways in Rats

“…Proinflammatory mediators, such as TNF- α and IL-1 β , rapidly released from injured tissue in the initial phase of hind limb I/R are known to play a crucial role in hind limb I/R injury [30]. These cytokines could recruit inflammatory cells and regulate the permeability of blood and lymphatic vessels and lead to endothelial dysfunction [31, 32].…”

Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson’s Disease: Rationale for Clinical Trial, and Current Progress

“…This supported earlier work by Tong et al [ 32 ] who had found in amyloid precursor protein transgenic mice that Simvastatin attenuated inflammation, oxidative stress and reduced amyloid beta levels and the number of affected neurites. Simvastatin had also been shown to protect against tissue injury in the context of ischemia-reperfusion injury [ 33 ], and in a model of cardiopulmonary bypass to protect against cerebral and systemic inflammation, neuronal loss and memory impairment [ 34 ].…”

Bilobalide protects against ischemia/reperfusion-induced oxidative stress and inflammatory responses via the MAPK/NF-κB pathways in rats

“…It has been reported that ischemic preconditioning [ 9 ], ischemic postconditioning [ 21 ], controlled reperfusion [ 22 ], hypothermia [ 23 ], light-emitting diode therapy [ 24 ] and some other physical therapies can relieve skeletal I/R injury [ 25 ]. In addition, several agents, such as dexamethasone [ 10 ], curcumin [ 26 ], salvianolic acid [ 8 ], silibinin [ 27 ], simvastatin [ 28 ], cyclosporine A [ 29 ], hydrogen-rich saline [ 30 ] and lipoxin A4 [ 4 ], have been shown to be effective in attenuating skeletal I/R injury. In cases of traumatic injuries in which I/R is not predictable and early intervention is desired, such strategies are not as relevant.…”