Four-aminopyrazolopyrimidine (4-APP)-induced fatty livers were studied immunohistochemically and biochemically. Immunohistochemical localization of glutathione-peroxidase (GSH-PO) in control rat liver was predominantly observed in the hepatocytes of portal zones of the hepatic lobules. After 3 days of 4-APP administration, the intensity of GSH-PO staining was weaker than that of control. Especially, this tendency was predominantly observed in portal zones of the hepatic lobules. Biochemcally, lipid peroxide levels measured by thiobarbituric acid method in the liver homogenates were markedly increased following 4-APP administration. However, glutathione-peroxidase (GSH-PO) activity in the same homogenates was decreased. Based on our data, we strongly suggested that pathogenesis of 4-APP induced-fatty liver may be due to uncontrolled free radical formation, peroxidation of lipids, and an associated lipid accumulation in the liver.
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Tokai J Exp Clin Med
September 2002
Safety Research Department, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Japan.
Four-aminopyrazolopyrimidine (4-APP)-induced fatty livers were studied immunohistochemically and biochemically. Immunohistochemical localization of glutathione-peroxidase (GSH-PO) in control rat liver was predominantly observed in the hepatocytes of portal zones of the hepatic lobules. After 3 days of 4-APP administration, the intensity of GSH-PO staining was weaker than that of control.
View Article and Find Full Text PDFAdrenocortical function in 4-APP-induced (4-aminopyrazolo[3,4-d]pyrymidine) lipoprotein-deficient rats was studied in relation to quantitative morphologic changes in the gland. 4-APP treatment results in enlargement of the adrenal cortex and its zona fasciculata and reticularis cells. In enlarged livers, cholesterol and free fatty acid concentrations were similar to that of control rats, however a marked accumulation of triglycerides with a concomitant drop in hepatic delta 4-steroid hydrogenase activity was found.
View Article and Find Full Text PDFTokai J Exp Clin Med
April 1985
Ultrastructural alterations of 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver were studied. Light microscopically, liver sections after 3 to 5 days of 4-APP administration demonstrated more extensive fatty changes and highly osmiophilic lipid droplets were mainly observed in the portal zones of the lobules. The most striking ultrastructural alterations were seen in the Golgi complexes and rough endoplasmic reticulum.
View Article and Find Full Text PDFActa Pathol Microbiol Scand A
January 1979
The influence of 4-aminopyrazolopyrimidine (4-APP) on morphology and on synthesis and secretion ability of isolated rat hepatocytes was investigated: 4-APP was found to inhibit both the synthesis and secretion of proteins. The synthesis of triglycerides was unaffected by 4-APP, while the secretion of triglycerides was markedly reduced. Transmission electron microscopy revealed that 4-APP induced morphological changes in the smooth membrane systems, the smooth endoplasmic reticulum and the Golgi apparatus.
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