| الوصف: |
The liver is particularly vulnerable to chemical-induced injury, owing to its central role in maintaining metabolic homeostasis and its location between the digestive tract and the rest of the body. Because venous blood from the stomach and intestines enters the liver via the portal vein prior to entering systemic circulation, the liver is the first organ to encounter ingested nutrients, vitamins, metals, drugs, and environmental chemicals, including waste products from intestinal bacteria. The first-pass exposure to drugs administered orally and the high capacity for xenobiotic metabolism are considered significant reasons why the liver is a target for drug toxicity, and this aspect has been widely reviewed (Park et al., 2005). Toxic metabolites can be generated and accumulate within hepatocytes as a result of oxidation–reduction (phase I), conjugation (phase II), and the saturation of transporter (phase III) reactions which normally serve to remove or detoxify xenobiotics (Park et al., 2005, 2011). Acute or chronic exposure to chemicals can detrimentally alter all or some of the key functions of the liver, including the scavenging or uptake processes that extract absorbed materials from the blood and process them via catabolism, storage, and/or biliary excretion. Such disruption can occur with or without appreciable cellular damage (Treinen-Moslen, 2001). As such, detection of chemically induced liver injury can be complicated and is largely reliant upon tests that measure integrity of liver cells as well as hepatic function. The primary purpose of this article is to discuss both established and emerging tests for the detection of hepatotoxicity in mammalian test species and in clinical practice. |
