Hepatocellular necrosis

Inhalation of 40 mg toxaphene dust/m3 for 3 months Slight hepatocellular necrosis 2... 

In the chronic inhalation bioassay of 1,2-dibromoethane conducted by NTP (1982) (discussed in Section 2.2.1.8), increased incidence of focal and centrilobular hepatocellular necrosis occurred in male and female F344 rats exposed to the highest dose (40 ppm) of 1,2-dibromoethane. Compound-related degenerative or necrotizing hepatocellular lesions did not occur in B6C3Fi mice following exposure to any concentration used. Liver lesions were not reported in rats after chronic inhalation exposure to 20 ppm 1,2-dibromoethane with or without 0.05% disulfiram in the diet however, hepatocellular tumors (not otherwise classified) were induced in exposed rats fed dietary disulfiram (Wong et al. 1982). Also see Section 2.2.1.8. 

Hepatocellular necrosis related to covalent binding of metabolites to cell and plasma proteins and to mitochondrial membrane damage results in release of intracellular enzymes into the bloodstream, providing biomarkers of liver cell damage. Biomarkers of hepatocellular necrosis are not specific to... 

Determination of the level of cytosolic enzymes such as aspartate transaminase, alanine transaminase, and lactate dehydrogenase is part of standard biochemical liver function tests to measure hepatocellular necrosis [2, 101]. Cytosolic enzymes are not subject to genetic variations inherent in microsomal enzyme production. Liver cytosolic enzymes metabolize several molecules, of which galactose and amino acids are typical examples, used for hepatic function tests. 

In recently completed inhalation studies, mice exposed at 80 ppm for 13 weeks had epithelial hyperplasia of the forestomach and rats exposed at 200ppm for the same duration had degeneration and metaplasia of the olfactory epithelium, anemia, hepatocellular necrosis, and reduced sperm motility."... 

Male and female mice exposed at 0, 25, 50, or 75 ppm 6 hours/day, 5 days/week for up 2 weeks had concentration-dependent changes in the olfactory epithelium hepatocellular necrosis was observed at the highest dose, and some male mice also had transient tubular damage in the kidneys. ... 

Thirteen-week inhalation exposure to ONCB in mice at doses ranging from 1.1 to 18 ppm caused hyperplasia of the forestomach, hepatocellular necrosis, secondary effects of methemoglobin formation on the spleen, liver, and bone marrow, and, at the highest dose, death. Rats similarly exposed had hyperplasia of the nasal cavity and, at the lowest dose tested, methemoglobinemia. 

Allergic reactions to drugs produce foci of necrosis that are scattered throughout the liver. Other agents cause severe (chlorpromazine) or mild (estrogens) cholestatic liver damage, including cholestasis and inflammation of the portal triad and hepatocellular necrosis. 

Thus, the hepatotoxicity of iproniazid and isoniazid may involve the alkylation or acylation of tissue proteins and other macromolecules in the liver. How these covalent interactions lead to the observed hepatocellular necrosis is at present not understood. 

Grasso P, Abraham R, Hendy R, et al. 1973. Hepatocellular necrosis from dietary silver in vitamin E-deficient rats [Abstract], J Pathol 100 ix. 

The latter is manifested by a reversible increase in serum AST or ALT levels of sufficient magnitude to require dose reduction or withdrawal in 40-50% of patients. Hepatocellular necrosis with jaundice has been reported. 

TCDD twice a week for 20 weeks (Hebert et al. 1990). Fatty degeneration and hepatocellular necrosis were observed in the livers of Swiss Webster mice exposed to 0.005 g 2,3,7,8-TCDD 3 days a week for 13 weeks (NTP 1982a). No hepatic effects were found in mice chronically exposed to... 

In addition to its effects on the promotion of ROS formation and fibrogenesis, iron is directly toxic to hepatocytes and causes hepatocellular necrosis (sideronecrosis). Iron also acts as a cofactor in the promotion of fibrogenesis by other hepatotoxins such as alcohol and viruses (Pietrangelo, 1998). 

GSH protection from APAP toxicity. Mitochondrial GSH depletion, peroxynitrite formation, and mitochondrial permeability transition appear to be critical for APAP hepatocellular necrosis. 

Isolated cases of chronic paracetamol toxicity have been reported, such as hepatocellular necrosis, hepatic inflammation and fibrosis. These cases occurred in patients taking 2-6 g of paracetamol daily for months... 

Domperidone may be the antiemetic of choice, but as the patient has very little metabolic and synthetic liver function, owing to massive hepatocellular necrosis secondary to the hepatotoxic effects of the paracetamol overdose, accumulation of the domperidone may occur. However, it may be of benefit as a pro-kinetic agent. 

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