The reversibility of increased rat liver weights and microsomal processing enzymes after feeding high levels of 2,2,4-trimethyl-1,3-pentanediol diisobutyrate

Abstract

2,2,4-Trimethyl-1,3-pentanediol diisobutyrate (TXIB) was fed to male and female albino rats at concentrations of 0.1 and 1.0% in the diet. In 3 experiments run concurrently, animals were fed the diets for (A) 52 days, (B) 99 days and (C) 52 days, then changed to a control diet for 47 days or fed a control diet for 52 days, then changed to the TXIB diet for 47 days. This design was adopted to determine whether increased liver weights previously seen with this compound were reproducible and reversible if the compound was with-drawn. Body weights, feed consumption, general appearance and behavior of all animals were recorded. Routine hematologic examinations, alkaline phosphatase and SGOT determinations were performed. Tissues were collected for histopathology, and selected organs were weighed for organ weight comparisons. Liver tissue was prepared for assay of the microsomal glucose-6-phosphatase, p-nitroanisole demethylase, UDP- p-aminophenol and UDP-bilirubin-β- d-glucuronyl transferase. The only consistent changes were an increasesin relative liver weights and increases in p-nitroanisole demethylase, UDP- p-aminophenol and bilirubin glucuronyl transferase. These changes occurred in both sexes, but only in the animals fed the high dose level and only when the animals were ingesting the compound at the time of sacrifice. These changes were not seen in animals fed the 1.0% diet for the first 52 days and the control diet the last 47 days. It appears, there-fore, that high doses of TXIB cause significant adaptive changes in the rat liver, and these changes are reversible if the animal is returned to a normal diet. Male rats given ip injections of 100 mg/kg TXIB or the parent glycol (TMPD ®) for 7 days had elevated demethylase activity when compared to the controls. This change was not seen at 25 mg/kg, and neither dose level of either compound affected the bilirubin glucuronyl transferase activity.