Prevention of cisplatin nephrotoxicity by exogenous atrial natriuretic peptide.
The ability of atrial natriuretic peptide (ANP) to prevent cisplatin-induced nephrotoxicity was compared to the protective effect of 3% NaCl. ANP (1 microgram/kg/min), 3% NaCl or peptide buffer vehicle (50 microliters/min) were infused for 45 min to conscious unrestrained rats immediately after cisplatin administration (5 mg/kg i.v.). Measurements taken 72 h after drug treatment indicated that compared to animals receiving cisplatin only, ANP co-treated rats had lower post-treatment plasma creatinine concentrations (0.70 +/- 0.07 vs 1.3 +/- 0.17 mg/dl; P < 0.05), blood urea nitrogen (BUN) concentrations (44.2 +/- 5.8 vs. 65.5 +/- 2.1 mg/dl; P < 0.05) and higher post-treatment glomerular filtration rates (GFR) (0.71 +/- 0.18 vs. 0.14 +/- 0.03 ml/min; P < 0.05). ANP was as effective as 3% NaCl in preventing cisplatin nephrotoxicity in this model. The effect of ANP co-treatment on the anti-tumor activity of cisplatin was also examined using the Walker 256 carcinosarcoma model. ANP treatment did not result in any observable loss in anti-tumor activity. When ANP was administered 72 h after cisplatin treatment, improvement in GFR was observed for the duration of the infusion, confirming the beneficial effect of ANP on cisplatin-damaged kidneys. ANP may have a role in the treatment and prevention of cisplatin nephrotoxicity especially in clinical situations where treatment with a large fluid volume is contraindicated.
Deegan
P M
PM
Department of Medicine, Vanderbilt University, Nashville, TN 37232-5536, USA.
Basinger
M A
MA
Jones
M M
MM
Hande
K R
KR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology
D000970:Antineoplastic Agents; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D002945:Cisplatin