[Cyclosporine induced nephrotoxicity and juxtaglomerular apparatus in mice].
To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological experiments using mice. Adult male ICR strain mice weighing about 40 g were used. The mice were divided into 2 groups: the Cs group (Cs 50 mg/kg/day was orally given for 14 consecutive days) and the control group (olive oil for 14 days). Urine was stored for 24 hours on the day 0, 7 and 14 and urine volume and concentrations of urinary creatinine (u-Cr) and urinary potassium (u-K) were measured in each group. All the mice were sacrificed and examined on the 15th day. Concentrations of serum creatinine (s-Cr), serum potassium (s-K), plasma renin activity (PRA), plasma aldosterone (Ald) were noted in each group. The kidneys were also examined histologically with light and electron microscopes. The Cs group showed significant increases of s-K, PRA and Ald and a significant decrease of creatinine clearance compared with the control group. Histologically, the Cs group demonstrated focal vacuolar changes in the proximal tubular cells and an increase in the number of granules in the JG cells. Each granule of the Cs group was larger than that of the control group. Cs certainly stimulates the renin-angiotensin-aldosterone system and causes consequently a secondary aldosteronism.
Ishikawa
A
A
Department of Urology, Hamamatsu University School of Medicine.
Sakaguchi
M
M
Nakano
M
M
Ushiyama
T
T
Ohta
N
N
Ohtawara
Y
Y
Tajima
A
A
Kawabe
K
K
Aso
Y
Y
D000818:Animals; D003404:Creatinine / Q000652:urine; D016572:Cyclosporine / Q000633:toxicity*; D006929:Hyperaldosteronism / Q000139:chemically induced; D007606:Juxtaglomerular Apparatus / Q000187:drug effects* / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011188:Potassium / Q000652:urine; D012083:Renin / Q000097:blood
D016572:Cyclosporine; D003404:Creatinine; D012083:Renin; D011188:Potassium