Hydronephrosis in rats associated with postnatal exposure to a fatty acid oxidation inhibitor.

Abstract

Methyl palmoxirate, an inhibitor of long-chain fatty acid oxidation, was administered by gavage (0, 1, 5, or 20 mg/kg/day) to female rats over the last third of gestation and throughout lactation. Weight gain (mid- and high-dosage group) and survivability (high-dosage group) were significantly (p less than or equal to 0.05) reduced in offspring of methyl palmoxirate-treated dams as compared to control offspring. Mid- and high-dosage male offspring found dead after Day 4 of lactation exhibited grossly distended bladders and renal pelves. A dosage-related increased incidence of dilated renal pelves was observed in both sexes at necropsy of 21-day-old mid- and high-dosage group pups. Microscopic examination of the urinary tracts of a number of affected pups revealed renal parenchymal atrophy and urethral obstruction. Drug disposition studies indicated lactating pups were exposed to significant amounts of methyl palmoxirate via mammary secretions. Cross-fostering experimentation suggested that some of the adverse effects observed in offspring were due to lactational, rather than in utero, exposure.

• Authors: M F Kenel, J H Krayer, K T Ng, C H Kircher
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 93 Issue 1 Pg. 127-36 (Mar 30 1988) ISSN: 0041-008X [Print] United States
• PMID: 3353998 (Publication Type: Journal Article)

Chemical References

• Epoxy Compounds
• Ethers, Cyclic
• Fatty Acids
• Propionates
• Proteins
• methyl 2-tetradecylglycidate

Topics

• Animals
• Blood Urea Nitrogen
• Dose-Response Relationship, Drug
• Epoxy Compounds (toxicity)
• Ethers, Cyclic (toxicity)
• Fatty Acids (metabolism)
• Female
• Hydronephrosis (chemically induced)
• Kidney (drug effects, pathology)
• Lactation
• Milk (metabolism)
• Oxidation-Reduction
• Pregnancy
• Propionates (toxicity)
• Proteins (metabolism)
• Rats
• Rats, Inbred Strains
• Urethra (drug effects)