Immunohistochemical and biochemical studies in 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver.
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.
Murakoshi
Masanori
M
Safety Research Department, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Japan.
Fukui
Norio
N
Takekoshi
Susumu
S
D000818:Animals; D001386:Azides; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001386:Azides; D005609:Free Radicals; C065795:4-azidophenylpropionamide; D005979:Glutathione Peroxidase