Effect of 5-aminolevulinic acid dose and estrogen on protoporphyrin IX concentrations in the rat uterus.

Abstract

To determine the in vivo dose-response relation between administered 5-aminolevulinic acid (ALA) and the concentration of protoporphyrin IX (PpIX) produced in rat uterine tissue, to determine the effect of estrogen on ALA-induced PpIX production in the rat endometrium and myometrium, and to determine the selectivity of ALA-induced PpIX production in uterine tissue. Ovary-intact female rats (n = 53) received a subcutaneous estradiol-17 beta (E2) implant. Three days later, ALA dissolved in saline (0, 1, 2.5, 10, 25, or 50 mg/100 microL) was injected into one uterine horn. Three hours after ALA administration, the uterus was removed and the endometrium was scraped from the myometrium. In a second study, rats (n = 35) were ovariectomized and 8 days later given either an E2 or sham implant. After 3 days of hormonal or sham priming, ALA (10 or 25 mg) was injected into the uterine horn 3 hours before hysterectomy. In both studies, PpIX was extracted in a methanol/ perchloric acid (1:1) solution and quantified spectrofluorometrically. Five-aminolevulinic acid increased PpIX concentrations in the endometrium and myometrium in a dose-dependent fashion. Twenty-five milligrams of ALA produced maximum PpIX concentrations in both the endometrium and myometrium. In the second study, sham-implanted ovariectomized rats had endometrial PpIX concentrations approximately two times higher than those in the estrogen-primed rats after doses of either 10 or 25 mg ALA. In the third study, the endometrium had two to three times higher PpIX concentrations than the myometrium at 1, 10, 25, and 50 mg of ALA. An in vivo dose-response relation was demonstrated between ALA and uterine production of PpIX, with maximum PpIX concentrations occurring after 25 mg of intrauterine ALA. Because estrogen was not required to convert ALA to PpIX, complete endometrial ablation may best be achieved with an unstimulated endometrium.