Involvement of Activated Polymorphonuclear Leukocytes in Galactosamine-Induced Hepatic Injury in Rats.

Abstract

This study attempted to elucidate the pathological role of peripheral blood polymorphonuclear leukocytes (PMNs) in the damage to hepatic sinusoidal endothelial cells (HSECs) in hepatic injury. Wistar male rats weighing about 200 g received a single injection of 1 g/kg body weight of galactosamine (GalN) intraperitoneally for the induction of hepatitis. The level of serum glutamic pyruvate transaminase activity increased time-dependently concomitantly with serum endotoxin level and hepatic lipid peroxide content. Histological studies using light and electron microscopy showed that a large number of PMNs infiltrated the midzonal area of the liver and that HSECs in contact with the PMNs were injured 6 h after GalN injection. Superoxide anion production by PMNs isolated from the peripheral blood of rats treated with GalN was increased significantly compared with that from control rats, as estimated by the reduction of exogenously added cytochrome c in the presence of phorbol myristate acetate. A cytotoxicity study using the 51Cr release assay revealed that PMNs isolated from GalN-treated rats caused more serious injury to the HSECs than those from control rats. These results suggest that the oxygen-derived free radicals released from the activated PMNs directly injure HSECs and lead to a disturbance of sinusoidal microcirculation, causing an extended liver cell necrosis in GalN hepatitis.

Effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on disruption of hepatic antioxidant defense systems in rats treated with d-galactosamine

“…Furthermore, the hepatic activities of antioxidant enzymes such as SOD, catalase, and GSH-px are known to decrease in rats treated with GAL (Korda, 1996). Several reports have shown an increase in hepatic lipid peroxidation with liver injury development in GAL-treated rats (Seçkin et al, 1995;Hino et al, 1994;Sun et al, 2003), although Mourelle and Meza (1989) have reported that hepatic lipid peroxide level begins to increase before the onset of liver injury in GAL-treated rats. In the present study, treatment of rats with GAL (500 mg/kg body weight) caused an increase in the hepatic concentration of TBARS, an index of lipid peroxidation, at 24 h, but not at 6 h, after hepatotoxin treatment, as shown in our previous report (Ohta et al, 2002).…”

“…These results also suggest that this preventive effect of TJ-15 on the disruption of hepatic antioxidant defense systems in GAL-treated rats may be involved in its preventive effect on the progression of GAL-induced liver injury. Hino et al (1994) reported that, in rats treated with GAL, neutrophil infiltration into the liver cells increased with the formation and progression of liver injury and that ROS, such as O 2 − , released from activated neutrophils infiltrating into the liver of GAL-treated rats caused the extension of liver cell necrosis. We have shown in rats treated with GAL (500 mg/kg body weight) that neutrophil infiltration into the liver cells occurs at an early stage of liver injury and is enhanced at a progressed stage of the injury (Ohta et al, 2002).…”

“…Several reports have shown an increase in lipid peroxidation in the damaged liver of rats treated with GAL (Shiratori et al, 1988;Mourelle and Meza, 1989;Hu and Chen, 1992;Seçkin et al, 1995;Hino et al, 1994;Korda, 1996;Ohta et al, 2002;Sun et al, 2003). In addition, there are reports showing that hepatic antioxidant defense systems associated with antioxidants such as GSH and ascorbic acid and antioxidant enzymes such as SOD, catalase, an enzyme to decompose H 2 O 2 to H 2 O and O 2 , and glutathione peroxidase (GSH-px), an enzyme to metabolize hydroperoxides to corresponding alcohols using GSH as a co-substrate, are disrupted in GAL-treated rats (Hu and Chen, 1992;Seçkin et al, 1995;Korda, 1996;Sun et al, 2003).…”