1. Structure-function relationships of protoporphyrin-induced liver injury.
- Author
-
Lee RG, Avner DL, and Berenson MM
- Subjects
- Animals, Bile metabolism, Bile Canaliculi drug effects, Bile Canaliculi ultrastructure, Cell Membrane drug effects, Cell Membrane ultrastructure, Dilatation, Pathologic, Dose-Response Relationship, Drug, Liver pathology, Liver ultrastructure, Microscopy, Electron, Microvilli drug effects, Microvilli ultrastructure, Perfusion, Rats, Rats, Inbred Strains, Staining and Labeling, Structure-Activity Relationship, Liver drug effects, Porphyrins toxicity, Protoporphyrins toxicity
- Abstract
To further define the pathogenesis of protoporphyric liver disease, perfused rat livers received varying doses of protoporphyrin, and aberrations of hepatic ultrastructure and function were correlated. Results indicated that the relative canalicular volume was equally increased in all protoporphyrin-perfused livers; however, bile flow was only minimally diminished at the smallest protoporphyrin dose employed. Protoporphyrin injured microvilli at the sinusoidal pole and reduced the surface density of the endoplasmic reticulum in a dose-related fashion. No crystalline or amorphous material was detectable, and only slight mitochondrial distortions occurred. Thus, cholestasis did not correlate with canalicular dilatation, the presence of crystalline material, or mitochondrial changes. Liver plasma membrane abnormalities appeared to correlate with functional defects and support a direct hepatotoxicity. Long-term protoporphyrin overload studies are needed to assess differences between hepatic and erythroid (parenteral) sources of protoporphyrin overproduction.
- Published
- 1984