LIVER INJURIES INDUCED BY FREE RADICALS

Abstract

Hepatic injuries induced by two free-radical mediated xenobiotics such as CCl₄ and AAPH were examined with light and electron microscopes. Administration of CCl₄ to male ICR mice resulted in disappearance of glycogen in the hepatocytes of centrilobular region within 1 hr. Seven hours after the CCl₄ injection, marked fatty degeneration and necrosis were restricted to hepatocytes around the central vein. Ultrastructurally, dissociation of ribosomes from rough surfaced endoplasmic reticulum, disappearance of glycogen particles, and accumulation of fat droplets were seen exclusively in hepatocytes located in centrilobular region. Lining cells of hepatic sinusoid were affected less severe than the hepatocytes. In contrast to CCl₄-poisoning, mice given AAPH in high dose, showed hepatic injuries in centrilobular, midzonal and periportal areas in a similar grade. Sinusoidal lining cells were most severely affected. Occasionally, the degenerated lining cells desquamated from the sinusoid. Fat droplets and degenerated mitochondria were frequently seen in almost all hepatocytes. AAPH attacks not only the liver but also other organs such as the kidney, heart, and thymus. Differences between the pathological features of both free radicals are resposible to sites of free radical generation.