Phagocytosis and Detoxification

Kupffer cells are reticuloendothelial cells resident in the liver sinusoids that scavenge damaged red blood cells (RBCs) and bacteria as they pass through. Therefore, they are also known as liver macrophages. While hundreds of millions of RBCs are removed by the reticuloendothelial system every minute, Kupffer cellslyse RBCs into heme and globin. Globin is further catabolized into polypeptide components for reuse. Heme is broken into biliverdin and iron. Biliverdin is converted to bilirubin and finally excreted in the bile. Iron is transported to the liver and spleen for storage and to the bone for hematopoiesis.

Hepatocytes help the body eliminate xenobiotics (toxins) by transforming them into more excretable polar compounds through a two-step process. In PHASE I (Biotransformation), cytochrome p450 liver enzymes and NADPH-cytochrome c reductase catalyse hydrolysis, reduction and hydroxylation of the xenobiotic. These chemical reactions add or expose functional groups on the substance. This prepares it for conjugation with a polar, water soluble substance. PHASE II (Conjugation) liver enzymes such as glucuronosyltransferase, sulfotransferase, glutathione-S- transferase and acetyltransferase add glucuronide, sulfate, glutathione or acetyl adducts to the functional group making the conjugate more water soluble and more easily excreted in the urine and feces. In general, Phase I and Phase II reactions serve to minimize the accumulation of foreign substances by increasing their water solubility and excretion. However, these reactions may also transform some xenobi- otics from a non-toxic substance to a toxic metabolite. Production of toxic metabolites within the liver can cause hepatic injury.

< Prev   CONTENTS   Source   Next >