Centrilobular

F 23.4 F (increased liver weight centrilobular enlargement, increased serum lipids and cholesterol) ... 

This benign autosomal recessive disorder consists of conjugated hyperbilirubinemia in childhood or during adult life. The hyperbilirubinemia is caused by mutations in the gene encoding MRP-2 (see above), the protein involved in the secretion of conjugated bilirubin into bile. The centrilobular hepatocytes contain an abnormal black pigment that may be derived from epinephrine. 

Substantial toxic effects in the liver have been seen in acute studies in animals. Prout et al. (1985) administered single doses of 10-2,000 mg/kg trichloroethylene to rats and mice. Blood level kinetics of trichloroethylene and its metabolites revealed that trichloroethylene was metabolized more quickly in the mouse, and thus, at high doses, the mouse was exposed to greater concentrations of trichloroethylene metabolites than the rat. Hepatic hypertrophy and centrilobular swelling were observed in mice treated with... 

Inomata, T., Rao, G.A. and Tsukamoto, H. (1987). Lack of evidence for increased lipid peroxidation in ethanol-induced centrilobular necrosis of rat liver. Liver 7, 233-239. 

Tsukamoto, H. and Bacon, B.R, (1987). Status of pro and antioxidants in ethanol-induced centrilobular necrosis. Heptology 7, 1078. 

Tsukamoto, H. and Xi, X.P. (1989). Incomplete compensation of enhanced hepatic oxygen consumption in rats with alcoholic centrilobular necresis. Hepatology 9, 302-306. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Weanlings died from extensive centrilobular necrosis... 

Intratracheal injection of Pb carbonate at doses of 50-135 mg Pb/kg BW for 29 to 362 days 73% dead (11/15) with total dose of 1250-7800 mg lead. Before death, some animals lost weight, became increasingly aggressive, had hepatic centrilobular necrosis, were uncoordinated and weak, and had convulsions the blood had up to 62 mg Pb/L 22... 

Parenchymal changes affect the gas-exchanging units of the lungs (alveoli and pulmonary capillaries). Smoking-related disease most commonly results in centrilobular emphysema that primarily affects respiratory bronchioles. Panlobular emphysema is seen in AAT deficiency and extends to the alveolar ducts and sacs. 

The liver is sensitive to hexachloroethane following both acute and longer term exposure scenarios. Evidence of effects on the liver include increased weight and centrilobular necrosis in rats and rabbits and increased serum levels of liver enzymes in sheep. There can also be fatty degeneration of the tissues and hemorrhage when damage is severe. 

Liver necrosis is another concern following hexachloroethane exposure. Hexachloroethane is metabolized in the centrilobular area of the liver by way of the microsomal mixed function oxidase system. The relatively nonpolar pentachloroethyl free radical is an intermediate in this pathway. The reaction of the free radical with unsaturated lipids in the cellular or organelle membranes could contribute to hepatocyte damage and necrosis. 

Mendel) (F) Hepatic 0.1 (cloudy swelling of centrilobular cells) Endrin... 

Rabbit 24 hr Hepatic 94 F (centrilobular liver necrosis) Treon et al. 1955... 

This MRL for mirex was derived using a NOAEL of 0.075 mg/kg/day for dose-dependent hepatic changes from a study by NTP (1990). The dose-dependent changes included increased fatty metamorphosis (cytoplasmic vacuoles consistent with intracellular fat accumulation) and necrosis of hepatocytes (focal and/or centrilobular) in F344/N rats of both sexes at a dose of 0.7 mg/kg/day... 

M (increased liver weight centrilobular glycogen loss, marked fat accumulation, and some necrosis altered endoplasmic reticulum and enzyme activities)... 

Di-tt-octylphthalate has been shown to be a mild liver toxin at high doses in acute- and intermediate-duration studies in rodents. While the mechanism of action for these hepatic effects is not known, di-w-octylphthalate does not appear to behave like other phthalate esters such as di(2-ethylhexyl)phthalate, which have been shown to be hypolipidemic peroxisome proliferators. Instead, the liver changes associated with exposure to di- -octylphthalate are characterized by marked centrilobular accumulation of fat and loss of glycogen, accompanied by reduced glucose-6-phosphatase activity and some centrilobular necrosis. 

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