[Preventive effect of OP-41483-alpha-CD on cyclosporine A-induced renal tubular and arterial damages].
The aim of this study is to test whether a stable analogue prostaglandin I2 (OP-41483-alpha-CD) (OP) is effective to prevent Cyclosporine A (CsA)-induced nephrotoxicity. Male Lewis rats were administrated with CsA (50 or 100 mg/kg/day, per os) and treated with OP (25 micrograms/kg/day, subcutaneously). For the quantitativeness of qualitative changes, percent area of tubular vacuolization and the grade of renal arteriolar changes were evaluated at light microscopic level, then further examined under electron microscopy. CsA trough levels in the whole blood were also analyzed with HPLC and prostaglandin I2 was assayed by radioimmunoassay of its stable degeneration product 6-keto-PGF1-alpha. As a result, 1) ultrastructurally, perinuclear vacuoles in arteriolar media consisted of cellular intervaginated cytoplasmic processes of neighboring cells, suggesting spastic vasoconstriction induced by CsA, 2) survival rate of OP-treated rats were significantly high compared to that of rats with CsA alone, 3) pathologically, tubular and arterial damages were reduced in OP-treated models, 4) pharmacokinetic studies revealed that CsA trough levels were not different from those of CsA-received alone and OP-treated models, and 5) mean blood 6-keto-PGF1-alpha excretion in rats given CsA was higher than in normal rats.
Kobayashi
M
M
First Department of Surgery, Hirosaki University School of Medicine, Japan.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000627:therapeutic use*; D003524:Cyclosporins / Q000009:adverse effects* / Q000493:pharmacokinetics; D003912:Dextrins / Q000627:therapeutic use*; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D011863:Radioimmunoassay; D051381:Rats; D011917:Rats, Inbred Lew; D012077:Renal Artery / Q000187:drug effects* / Q000473:pathology; D013213:Starch / Q000627:therapeutic use*; D014617:Vacuoles / Q000648:ultrastructure; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D003524:Cyclosporins; D003912:Dextrins; D047391:alpha-Cyclodextrins; C051518:OP 41483-alpha-cyclodextrin; D015121:6-Ketoprostaglandin F1 alpha; D013213:Starch; D011464:Epoprostenol