Nephrotoxicity of fumaric acid monoethylester (FA ME).
The nephrotoxic actions of high single oral doses of fumaric acid monoethylester (FA ME) have been investigated in the rat. Fifty mg of this substance produced morphologic lesions of the glomeruli without reducing GFR. Following 100 mg, the lesions were more pronounced and GFR was diminished by about 40%. Despite of hemorrhages in kidney cortex the urines did not contain erythrocytes. Urinary protein was augmented in single cases only. Fifty to 100 mg FA ME induced a marked concentration defect after water deprivation. In parallel FA ME reduced lactate production from glucose by kidney inner medulla in vitro. After in vivo application, however, no morphologic lesions were found in this zone of the kidney. FA ME had no effect on oxygen consumption of kidney slices despite of proximal tubular lesions observed histologically after 100 mg orally. Thus, 100 mg of FA ME have distinct nephrotoxic effects in the rat.
Hohenegger
M
M
Institute of General and Experimental Pathology, University of Vienna.
Vermes
M
M
Sadjak
A
A
Egger
G
G
Supanz
S
S
Erhart
U
U
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D005650:Fumarates / Q000633:toxicity* / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007444:Inulin; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D008297:Male; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D005650:Fumarates; D007773:Lactates; D007444:Inulin; C061175:ethyl fumarate