Heterogeneous Liver Lobe Responses of Carbon Tetrachloride-Induced Hepatotoxicity in Male Rats Pretreated with Hepatic Enzyme-Inducing Agents

Abstract

The present study was designed to compare the susceptibility to carbon tetrachloride (CCl 4 )-induced hepatotoxicities of the different liver lobes of rats which had been subjected to pretreatment with phenobarbital sodium (PB) or β-naphthoflavone (BNF). A detailed investigation was done to determine whether the susceptibility to CCl 4 hepatotoxicities was correlated with hepatic cytochrome P450 (CYP) activities in the different liver lobes. Male Wistar rats were given a single oral administration of CCl 4 (0.1 mL/kg, dissolved in liquid paraffin) or vehicle alone following three daily intraperitoneal injections of PB (40 mg/kg, dissolved in sterile saline) or BNF (40 mg/kg, suspended in sesame oil). One day after the CCl 4 administration, all animals were necropsied, and liver samples were obtained from the left and median lobes. Each sample was used for histopathological examination and 7-alkoxycoumarin O-dealkylase activity assay to evaluate the CYP activity. All the CCl 4 -treated animals revealed typical liver damage, such as the presence of ballooning degeneration and necrosis in centrilobular hepatocytes. PB pretreatment remarkably enhanced the extent of the liver damage, which was greater in the median lobe than the left lobe. BNF pretreatment only slightly enhanced the extent of the liver damage, which was also greater in the median lobe. These results indicate the different susceptibilities of rat liver lobes to CCl 4 -induced hepatotoxicities enhanced by pretreatment with PB or BNF. Moreover, the heterogeneity of the CYP activities enhanced by PB pretreatment was closely correlated with the susceptibility to CCl 4 -induced hepatotoxicities in the different liver lobes, although that by BNF pretreatment was not. (J Toxicol Pathol 2004; 17: 223-230)

Lobe-Specific Heterogeneity and Matrix Metalloproteinase Activation after Ischemia/Reperfusion Injury in Rat Livers

“…Comparing the results using both sham and I/R rat, we found new information regarding the hepatic lobe heterogeneity. Unlike in the reports of Uehara et al (2004), the functional lobe heterogeneity has been evaluated in the CCl4 toxicity induced to the whole liver. The functional differences between the right and median lobes have not been evaluate in case of I/R injury but will be considered in the future experiments.…”