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

Toxicol Appl Pharmacol. 1988 Mar 30;93(1):127-36. doi: 10.1016/0041-008x(88)90032-4.

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.

MeSH terms

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

Substances

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