Effects of 4-aminopyrazolo (3,4-d) pyrimidine on rat hepatocytes: an ultrastructural morphometric study.
The prolonged administration of the hypolipidemic drug 4-aminopyrazolo (3,4-d) pyrimidine (4APP) induced conspicuous morphological changes in rat hepatocytes, which are clearly demonstrated by stereology. We observed a significant decrease in the rough endoplasmic reticulum, and an accumulation of lipid droplets, which was coupled with a comparable rise in the hepatic concentrations of total cholesterol and triglycerides. These changes were interpreted as the expression of the 4APP-provoked impairment of the synthesis of the polypeptide chains of lipoproteins and of the consequent suppression of the assembly of lipid molecules in exportable lipoproteins. We also noted a neto lowering in smooth endoplasmic reticulum and peroxisomes, a decrease which was hypothesized to be the morphological counterpart of a reduced de novo cholesterol synthesis, due to the 4APP-induced rise in the intracellular cholesterol concentration.
Belloni
A S
AS
Department of Anatomy, University of Padua, Italy.
Rebuffat
P
P
Neri
G
G
Mazzocchi
G
G
Meneghelli
V
V
Nussdorfer
G G
GG
D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D000924:Anticholesteremic Agents / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D002784:Cholesterol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling
D000924:Anticholesteremic Agents; D008074:Lipoproteins; C004420:4-aminopyrazolo(3,4-d)pyrimidine; D002784:Cholesterol; D000225:Adenine