The hepatotoxic action of allyl formate

Abstract

The hepatotoxic action of allyl formate on rat liver has been investigated. Biochemical changes can be detected in the liver cell many hours before the histological changes and it would appear that the toxin has a direct action on the liver parenchymal cell. The results suggest that allyl formate is not the toxic agent but that it is converted via allyl alcohol into acrolein. This reaction requires the presence of alcohol dehydrogenase. Histochemical studies have shown that this enzyme is localized in the periportal region of the liver lobule, and may explain why allyl formate solely produces a periportal necrosis. As glutathione and 1,4-dithiothreitol protect against the early biochemical changes produced by the poison, it is probable that acrolein alkylates proteins and nucleic acids.

Possible Mechanism of Liver Necrosis Caused by Aromatic Organic Compounds

“…It should be pointed out that these hepatotoxic agents are activated by enzymes other than those in endoplasmic reticulum. In fact, Rees and Tarlow (24) have shown that allyl formate is converted to the highly reactive aldehyde, acroleia, by alcohol dehydrogeniase and that this enzyme is localized in the periportal zone.…”

“…In a typical experiment, the histology of a normal liver (Fig. 1A) was compared with that of a liver from a rat injected with bromobenzene (0.2 ml) 24 Prior treatment of animals with phenobarbital markedly increased the centrolobular hepatotoxicity of a number of aromatic hydrocarbons. For example, a low dose of bromobenzene (0.03 ml), which caused little toxicity in untreated animals ( Fig.…”

“…in 0.5-2 ml of sesame oil). 24 hr later, the livers were removed and slices 1-2 mm thick were fixed in buffered formalin, dehydrated in graded strengths of ethanol, cleared in xylol, and embedded in paraffin. Sections (6 /Am thick) were stained with periodic acid-Schiff reagent (PAS) and hematoxylin (5 Harris's hematoxylin (6).…”

Partial Separation and Biochemical Characteristics of Periportal and Perivenous Hepatocytes from Rat Liver

“…Large differences were found for alanine aminotransferase [4-61, lactate dehydrogenase [4,6], pyruvate kinase and phosphoenolpyruvate carboxykinase [7], glucokinase and fructose-l,6-bisphosphatase [8], and glucose-6-phosphatase [9]. Changes in the hepatic content of glycogen due to nutritional variation [lo, 1 I], or hepatic damage due to administration of xenobiotics [12,13], also occurred in different zones along a porta-cava line. Furthermore, cell necrosis due to chronic ethanol consumption starts in perivenous hepatocytes [I], but as to the localization of alcohol dehydrogenase the results were conflicting [14, 151.…”

Formação de adutos exocíclicos com bases de DNA: implicações em mutagênese e carcinogênese

“…Dentre os trans-2-alcenais, os mais estudados são acroleína [H 2 C=CH-HC=O] e crotonaldeído [H 3 C-CH=CH-HC=O]. Eles são formados endogenamente como resultado da oxidação de lipídios 132 , aminoácidos 162 e poliaminas 224 e ocorrem no ambiente como componentes da fumaça de cigarro (acroleína: 10-140 µg/cigarro) e exaustão de automóveis, sendo também produzidos quando alimentos contendo gordura são cozidos 132,225,226 ; ocorrem também como produtos do metabolismo de drogas 224,[227][228][229] , carcinógenos (ex. : N-nitrosopirrolidina origina crotonaldeído) e agentes quimioterapêuticos (ex.…”