Vitamin A metabolism is altered in brown Norway and long-Evans rats infused with naftidrofuryl or erythromycin intravenously.
Enzymatic retinyl ester hydrolysis is a key reaction for maintaining cellular retinol homeostasis. The ability of naftidrofuryl and erythromycin to inhibit retinol liberation by retinyl ester hydrolase (REH) in vitro suggests an ability to interfere with vitamin A metabolism in vivo, particularly during hepatic processing. To address this question, systemic and local response to these agents were studied in Brown Norway (BN) and Long-Evans (LE) rats. The study was conducted in two parts: a drug-loading phase and a washout phase. Analysis of variance of the time course changes in plasma retinol during the post-treatment period (Days 10-18) showed rat strain (p < 0.04) and time (p < 0.001; strain-by-time interactive effect, p < 0.001) to be significant factors, but drug exposure (p = 0.19) was not significant. Endpoints included hepatic REH activity, size and composition of the liver vitamin A stores, and retinoid content of the kidneys. Rats recovering from naftidrofuryl dosing demonstrated a lower REH activity than did animals recovering from erythromycin treatment (p < 0.009). The major side effect of erythromycin is vitamin A accumulation in the liver (p < 0.001) and reductions in retinol reserves (p < 0.02) were among the consequences of naftidrofuryl treatment. In the kidney of LE rats, there were higher concentrations of vitamin A (p < 0.003) secondary to naftidrofuryl exposure. Together our data suggest that clinically achievable concentrations of the drugs, given as a continuous infusion, produce aberrations in vitamin A metabolism.
Schindler
Rainer
R
Department of Human Nutrition and Food Science, Düsternbrooker Weg 17, Christian-Albrechts-University, D-24116 Kiel, Germany. RuHSch@aol.com
Fielenbach
Tanja
T
Rave
Gerhard
G
Blömer
Anne
A
Kellersmann
Richard
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009257:Nafronyl / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D020318:Rats, Long-Evans; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D014801:Vitamin A / Q000097:blood / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000139:chemically induced
D000900:Anti-Bacterial Agents; D014665:Vasodilator Agents; D014801:Vitamin A; D009257:Nafronyl; D004917:Erythromycin; D002265:Carboxylic Ester Hydrolases; C022523:retinyl esterase