Inability of nitrendipine to protect against gentamicin nephrotoxicity in the rat.
Daily sc injection of gentamicin (100 mg/kg) for 4 days produced a significant decrease in the activities of renal cortical Na+,K+-ATPase and alkaline phosphatase. The observed reduction in renal functional enzymatic markers was associated with significant elevation in sphingomyelin, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylcholine, and total phospholipid. Gentamicin significantly decreased the activity of renal phospholipase C. Nitrendipine (25 mg/kg/day) for 7 days po for 4 days alone did not markedly alter the activities of kidney phospholipase C, alkaline phosphatase, and Na+,K+-ATPase or tissue phospholipid levels. Daily administration of nitrendipine for 3 days followed by concurrent treatment of nitrendipine and gentamicin failed to prevent antibiotic-induced renal histopathologic changes, phospholipidosis, or decrease in alkaline phosphatase. However, in rats simultaneously given nitrendipine and gentamicin the activity of Na+,K+-ATPase returned to control values, indicating a selective blocking action for nitrendipine. The inability of nitrendipine to prevent gentamicin-induced renal phospholipidosis or decreases in enzymatic function markers was associated with significantly elevated tissue aminoglycoside levels when compared to values seen in rats given only the antibiotic. Evidence suggests that nitrendipine is not effective in lowering the concentration of gentamicin in renal cortex. The effectiveness of an agent in providing protection against aminoglycoside nephrotoxicity may be associated with the ability of the drug to lower renal gentamicin content.
Kacew
S
S
Department of Pharmacology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
D000818:Animals; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007672:Kidney Cortex / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D005839:Gentamicins; D010743:Phospholipids; D009568:Nitrendipine; D010738:Type C Phospholipases; D000254:Sodium-Potassium-Exchanging ATPase