Reduced aminolevulinate dehydrase activity in rats with functional renal failure induced by cyclosporin A.
Patients with chronic failure evidence various abnormalities in heme metabolism, primarily erythrocyte aminolevulinate dehydrase hypoactivity and increased plasma and erythrocyte porphyrin levels. Such abnormalities have also been observed in animals with both acute and chronic experimental renal failure. The aim of this work was to study these parameters of porphyrin metabolism in an experimental model of functional renal failure. A group of 11 male Wistar rats received 13 doses (25 mg/kg body weight/day) of cyclosporin A. Serum creatinine did not vary, but the blood urea nitrogen levels increased and a significant decrease in the creatinine clearance was observed. The drug also caused a marked decrease in the erythrocyte aminolevulinate dehydrase activity, a slight reduction of the hematocrit value, and increased levels of blood porphyrins. The plasma of treated rats showed capacity to inhibit aminolevulinate dehydrase activity when incubated in vitro with erythrocytes from control rats. Porphyrin metabolism remained unchanged in the liver. The daily diuresis was significantly decreased in the cyclosporin as compared to the control group; however, the porphyrinuria showed no changes. The derangements in the erythrocyte heme biosynthesis pathway observed in patients with chronic renal failure are reproducible in an experimental model of cyclosporin A-induced functional renal failure.
Fontanellas
A
A
Porphyria Unit, Hospital Universitario Doce de Octubre, Madrid, Spain.
Herrero
J A
JA
Enríquez de Salamanca
R
R
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004912:Erythrocytes / Q000201:enzymology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006418:Heme / Q000096:biosynthesis; D007668:Kidney / Q000201:enzymology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D000623:Porphobilinogen Synthase / Q000097:blood*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D011166:Porphyrins; D006418:Heme; D016572:Cyclosporine; D000624:5-Aminolevulinate Synthetase; D000623:Porphobilinogen Synthase