Evidence that cyclosporine causes both intracellular migration and inappropriate urinary excretion of magnesium in rats.
We determined the effects of cyclosporine on calcium, magnesium, and potassium metabolism in rats. Thirty Sprague-Dawley rats were randomized into three groups of ten animals each--control rats given olive oil, rats given cyclosporine at a dosage of 5 mg/kg daily, and rats given 15 mg/kg daily for four weeks. Urinary excretion of calcium, magnesium, and potassium was determined before and after 2 and 4 weeks of cyclosporine therapy. All rats were sacrificed after 4 weeks of therapy, and calcium, magnesium, and potassium concentrations in serum and tissues were determined. Serum magnesium levels were significantly lower in the cyclosporine-treated groups than in the control group, but there was no significant difference between the control and either of the cyclosporine-treated groups with regard to total urinary excretion of magnesium after four weeks of treatment. Magnesium content in the kidney, muscle, and liver was significantly higher in the 15 mg/kg group than in the control group. Calcium content in the kidney and liver was significantly higher as well. Potassium content in any type of tissue was similar in the three groups. We conclude that the intracellular migration of magnesium plays an important role--as does impaired renal conservation of magnesium--in the pathogenesis of cyclosporine-induced hypomagnesemia and that there is a discrepancy between magnesium and potassium metabolism in cyclosporine-treated rats.
Nozue
T
T
Department of Pediatrics, Showa University, Toyosu Hospital, Tokyo, Japan.
Kobayashi
A
A
Sako
A
A
Satoh
T
T
Kodama
T
T
Yamazaki
H
H
Kurosawa
M
M
Uemasu
F
F
Endoh
H
H
Takagi
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism* / Q000652:urine; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016572:Cyclosporine; D008274:Magnesium; D011188:Potassium; D002118:Calcium