Tissue lesions liver necrosis

2 TISSUE LESIONS LIVER NECROSIS 7.2.1 Carbon Tetrachloride 

This solvent, once used extensively in dry cleaning and even as an anesthetic is primarily hepatotoxic, causing two different types of pathological effect. The hepatotoxicity of carbon tetrachloride has probably been more extensively studied than that of any other hepatotoxin, and there is now a wealth of data available. Its toxicity has been studied both from the biochemical and pathological viewpoints, and therefore the data available provide particular insight into mechanisms of toxicity. 

Carbon tetrachloride is a simple molecule which, when administered to a variety of species, causes centrilobular hepatic necrosis (zone 3) and fatty liver. It is a very lipid-soluble compound and is consequently well distributed throughout the body, but despite this, its 

The first events occurring after a toxic dose of carbon tetrachloride can be observed or detected biochemically around the endoplasmic reticulum. Within one minute of dosing, carbon tetrachloride is covalently bound to microsomal lipid and protein in the ratio of 11 3. Conjugated dienes, indicators of lipid peroxidation, can be detected in lipids within five minutes. 

The damage to the endoplasmic reticulum leads to loss of ability to synthesize proteins. This is carried out in the rough endoplasmic reticulum, whereas CYP2E1 activation takes place nearby in the smooth endoplasmic reticulum. 

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The lesions produced in avitaminosis E vary greatly, depending upon the animal used for the experimentation. The pathological observation can be classified into four main groups interference with reproduction muscular degeneration pigment formation in adipose tissue and liver necrosis. 

A systematic series of studies on the ECT of pig liver have appeared from the Australian group of Maddern et al. Electrolysis was investigated for generating areas of hepatic necrosis in the pig liver.88 The lesions healed with time and were associated with minimum morbidity. Further work on 21 pigs showed that during ECT of the liver tissue the electrolytic dose (in coulombs cm"3) correlated with the volume of liver necrosis.89 This group also established that in addition to the coulombic dose, pH could be used as a realtime monitor to predict more accurately the extent of necrosis. 

Liver Acetaminophen Increased mortality, increased serum transaminase levels, greater depletion of GSH, increased tissue lesions, increased centrilobular hepatic necrosis Chan et al. (2001) Enomoto et al. (2001)... 

No studies were located in humans regarding the distribution of 1,2-dibromoethane after oral exposure. In humans intentionally ingesting 1,2-dibromoethane, kidney lesions and centrilobular necrosis of the liver were found (Olmstead 1960 Saraswat et al. 1986). This is indirect evidence of distribution of 1,2-dibromoethane. The tissue distribution of 1,2-dibromoethane has been studied in rats following exposure by the oral route. Although retention was limited, the kidneys, liver, and spleen appear to retain the highest amounts of the administered dose (Plotnick et al. 1979) as illustrated in Table 2-4. Rats received an oral dose of 15 mg/kg/day of labeled 1,2-dibromoethane in corn oil. Twenty-four hours later 3% of radioactivity was detected in fat, brain, kidney, liver, spleen, testes, blood, and plasma, 72.38% in the urine, and 1.65% in the feces (Plotnick et al. 1979). By 48 hours after administration, 73% of the radiolabeled dose was accounted for in the urine, 1.1% in the liver, and 2.4% in the feces. Total recovery was 77.8% of the administered radioactivity. 

When administered by intraperitoneal injection, azaspiracid cattsed similar lesions to those reported for oral administration Besides fatly liver and necrosis of lymphoid tissues, i.p. administration to mice induced netrrologic symptoms that included spasm and paralysis of the limbs (Ito et al. 1998). 

Liver is the target organ for aflatoxins, and aflatoxicosis leads to proliferation of the bile duct, centrilobular necrosis and fatty infiltration of the liver, hepatomas and hepatic lesions. The susceptibility of animals to AFB] varies with species [reviewed in Eaton and Groopman, 72]. In addition to the liver, AFB] also affects other organs and tissues, such as the lungs and the entire respiratory system [73-75]. 

Cholecalcifefol toxicosis is best cotrfirmed by sampling of renal or hepatic tissue. Poisoning by cholecalciferol is usually delayed at least 24 hours, so stomach contents are ml representative. Wamin D metabolism takes place initially in the liver and then in the kidney, and the lesions of tubular necrosis and tissue calcificatirxi are prominent in the kidney. 

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