Periportal hepatocytes

Hadassah bred) Hepatic 29 (scattered hemorrhagic areas of necrosis, increased ALT, degeneration of hepatocytes, periportal infiltration with inflammatory cells, microthrombi in portal veins) 1972... 

Portal infusion of NAPQl into rats and mice produces necrosis in the periportal region (unpublished results quoted by Nelson, 1990). Studies of cultured hepatocytes sensitized to paracetamol by the induction of cytochrome P450 by 3-methylcholanthrene have shown that paracetamol-induced cytotoxicity was dependent on ROM generation (Gerson et al., 1985). 

F (centrilobuiar hepatocyte necrosis and severe diffuse vacuolar degeneration of midzonal and periportal hepatocytes)... 

Mouse 3wk Hepatic 34 M 90 M (centrilobular hepatocyte 138 M (centrilobular and periportal Larson et ai. 1994d... 

The MRL was based on a hepatic NOAEL of 3 ppm chloroform administered for 6 hours a day for 7 consecutive days to mice (Larson et al. 1994c). Female mice exposed to 100 or 300 ppm exhibited centrilobular hepatocyte necrosis and severe diffuse vacuolar degeneration of midzonal and periportal hepatocytes, while exposure to 10 or 30 ppm resulted in mild-to-moderate vacuolar changes in centrilobular hepatocytes. Decreased eosinophilia of the centrilobular and midzonal hepatocyte cytoplasm relative to periportal hepatocytes was observed at 30 ppm. Livers of mice in the 1 and 3 ppm groups did not differ significantly from control animals and were considered to be NOAELs for liver effects. The NOAEL of 3 ppm was converted to the Human Equivalent Concentration (HEC) as described in Equation 4-10 in Interim Methods for Development of Inhalation Reference Concentrations (ERA 1990b). This calculation resulted in a NOAEL hec] of 3 ppm. An uncertainty factor of 30 (3 for extrapolation from animals to humans and 10 for human variability) was applied to the NOAEL hec] value, which resulted in an MRL of 0.1 ppm. 

The liver is unusual in that it receives blood from two sources, the hepatic artery and the hepatic portal vein. The two supplies eventually join at the central vein, hence hepatocytes are of two types those which are exposed to blood derived largely from the hepatic artery, known as the perivenons cells, and those that are exposed to blood largely from the portal vein which are known as periportal cells (see Chapter 8). The periportal hepatocytes contain the enzymes of the ornithine cycle. In contrast, the... 

Basis for differences in carbon tetrachloride effects on periportal and pericentral hepatocytes enzymic and metabolic variations. 

After a single dose of ethionine, triglycerides accumulate in the liver, the increase being detectable after four hours. After 24 hours, the accumulation of triglycerides is maximal, being 15 to 20 times the normal level. Initially, the fat droplets accumulate on the endoplasmic reticulum in periportal hepatocytes and then in more central areas of the liver. Some species develop hepatic necrosis as well as fatty liver, and nuclear changes and disruption of the endoplasmic reticulum may also be observed. 

Figure 4-1. Photomicrograph of periportal hepatocytes of liver from patient in case report. Note variation in size and presence of cytoplasmic globules. The stain used is periodic acid-Schiff after diastase.

Benzene is metabolized primarily in the liver by the cytochrome P-450 system (Parke 1989). It appears that the metabolism of benzene by the hepatic cytochrome P-450 system plays an important role in its bioactivation and toxicity. Sammett et al. (1979) provided corroborative evidence of this by showing that partial hepatectomy of rats diminished both the rate of metabolism of benzene and its toxicity. An increase in altered hepatic foci has been shown in male rats after benzene exposure in conjunction with initiator and promotor administration (Dragan et al. 1993). A dose of 500 mg/kg of benzene administered subcutaneously once daily, 5 days a week for 26 weeks to Wistar rats resulted in focal fine droplet fatty metamorphosis with accompanying lymphoidal infiltration in the liver after 12 weeks (Bloch et al. 1990). In some cases a proliferated histocyte-like cells formed clusters in the vicinity of the periportal fields. After 26 weeks, more diffuse steatosis, feathery degeneration of hepatocytes, single necrotic cells were seen. 

Hepatic Fibrosis/Cirrhosis Fibrosis usually results from chronic inflammation which can be the result of continuous exposure to a variety of hepatotoxic chemicals such as organic arscnicals, vinyl chloride, or high doses of vitamin A (Zimmerman, 1999), chronic ethanol ingestion and nonalcoholic fatty liver disease. Fibrosis usually occurs around the portal area, in the space of Disse, and around the central veins. This results in loss of liver architecture and function. The hepatocytes are replaced with fibrous material and thus there is hepatocyte loss. Periportal fibrosis may lead to portal hypertension. 

Hepatocytes display metabolic heterogeneity according to their zonal location within the acinus. (42) (s. p. 24) Specific chemical processes thus proceed exclusively or predominantly in the hepatocytes of the periportal or the perivenous zones. The zonally segregated reactions may also be regulated separately. It seems that, under certain conditions, metabolic processes are also shifted from one zone of the acinus to another. 

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