Biomaterial Database

Furosemide induced hepatotoxicity. 1981

R M Walker, and T F McElligott

Furosemide-induced (400mg/kg ip) hepatotoxicity progressing to centrilobular necrosis was studied by light and electron microscopy in Swiss white mice. Centrilobular glycogen depletion and cytoplasmic foaminess, usually accompanied by extensive vacuolation, were detectable by light microscopy 1 1/2 hr after furosemide. Centrilobular congestion and hydropic single cell necrosis developed after 3 hr. Electron microscopy revealed disaggregation of polyribosomes, vesiculation of endoplasmic reticulum, an endocytic origin for the vacuolation, and a definite sequence in the development of congestion. Vacuolation coincided with loss of microvilli and resulted in detachment of sinusoidal lining cells from hepatocytes. Small vacuoles apparently formed at the sinusoidal margin of hepatocytes by fusion of microvilli. Congestion and occlusion of sinusoidal lumens developed as a consequence of erythrocytes entering the enlarged Disse space, possibly through pores in the lining cells, and thence entering endocytic vacuoles. The vacuolation, loss of microvilli and terminal hydropic degeneration suggest an important role for the plasma membrane in the development of furosemide-induced hepatotoxicity. Comparisons with known membrane toxins support this concept.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008107	Liver Diseases	Pathological processes of the LIVER.	Liver Dysfunction,Disease, Liver,Diseases, Liver,Dysfunction, Liver,Dysfunctions, Liver,Liver Disease,Liver Dysfunctions
D008297	Male		Males
D008854	Microscopy, Electron	Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.	Electron Microscopy
D009336	Necrosis	The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005665	Furosemide	A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.	Frusemide,Fursemide,Errolon,Frusemid,Furanthril,Furantral,Furosemide Monohydrochloride,Furosemide Monosodium Salt,Fusid,Lasix
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014617	Vacuoles	Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.	Vacuole
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus