Protective effects of cyclodextrin sulphates against gentamicin-induced nephrotoxicity in the rat.
The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied. Daily subcutaneous injection of gentamicin (100 mg kg-1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex. When cyclodextrin sulphates were given intraperitoneally at 300 mg kg-1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective. Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity. These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment.
Uekama
K
K
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Shiotami
K
K
Irie
T
T
Ishimaru
Y
Y
Pitha
J
J
D000818:Animals; D003505:Cyclodextrins / Q000627:therapeutic use*; D005839:Gentamicins / Q000633:toxicity*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects; D008297:Male; D009399:Nephrons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013431:Sulfates / Q000627:therapeutic use; D014508:Urea / Q000097:blood
D003505:Cyclodextrins; D005839:Gentamicins; D013431:Sulfates; D014508:Urea