الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Acute liver injury (ALI) is a common clinical event that disrupts liver homeostasis, leading to unacceptably high morbidity and mortality. Ischemia/reperfusion (I/R) injury is a pathophysiologic process in which cellular damage is accentuated following oxygen delivery to the ischemic tissue.
Hepatic ischemia/reperfusion injury (HIRI) remains the major cause of ALI that is observed in a variety of clinical situations such as liver transplantation and hepatic resection. It is believed that I/R-mediated hepatic injury has been resulted from both oxidative stress mediators including reactive oxygen/nitrogen species and also from the release of pro-inflammatory cytokines.
In ischemic acute liver injury, hypoxic cell injuries occur early during the ischemic phase, followed by inflammatory responses in the reperfusion phase. During reperfusion, re-oxygenation of the ischemic tissue generates various reactive oxygen species (ROS), which further contribute to profound hepatocellular injury—a phenomenon known as reperfusion injury.
During an acute inflammatory state, stimuli cause monocytes to release cytokines as TNF-α which up regulates the formation of chemokines as MCP-1 which is a potent chemokine that facilitates the recruitment of neutrophils and macrophages to inflammatory sites, which in turn, release reactive oxygen species (ROS). Oxidative stress occurs when a balance is disrupted by excessive production of ROS and/or by inadequate antioxidant defenses, including SOD and GPx. Reactive oxygen species (ROS) can also enhance lipid peroxidation of mitochondrial and plasma membranes which is indicated by increasing of malondialdehyde (MDA) content.
The current study was focused on evaluating the protective antioxidant and anti-inflammatory effects of tramadol and some natural products particularly limonin and baicalein against hepatic I/R-induced injury, In addition to investigating the possible underlying pathophysiological mechanisms that may be involved in I/R injury. The study also gave some insight on the possible involvement of toll like receptors and their mediators in hepatic I/R injury and the hepatoprotective role of limonin as an example.