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Effect of 5-Aminolevulinic Acid Dose and Estrogen on Protoporphyrin IX Concentrations in the Rat Uterus

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Abstract

Objectives

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.

Methods

Ovary-intact female rats (n = 53) received a subcutaneous estradiol-17β (E2) implant. Time days later, ALA dissolved in saline (0, 1, 2.5, 10, 25, or 50 mg/100 μL) was injected into one uterine horn. Time 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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Department of Physiology and the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Queen’s University, Kingston, ON, Canada, K7L 3N6

    Brenda N. Roy MSc, Dean A. Van Vugt PhD, Glenn E. Weagle PhD, Roy H. Pottier PhD & Robert L. Reid MD

  2. Department of Chemistry and Chemical Engineering, The Royal Military College of Canada, Kingston, Ontario, Canada

    Brenda N. Roy MSc, Dean A. Van Vugt PhD, Glenn E. Weagle PhD & Roy H. Pottier PhD

Authors
  1. Brenda N. Roy MSc
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  2. Dean A. Van Vugt PhD
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  3. Glenn E. Weagle PhD
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  4. Roy H. Pottier PhD
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  5. Robert L. Reid MD
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Additional information

Supported by DUSA Pharmaceuticals, Inc., Toronto, Ontario, and the Medical Research Council of Canada.

The authors wish to acknowledge Dr. Eva F. Gudgin Dickson for her helpful comments on the manuscript and Dr. S. Shin for the use of his laboratory facilities.

This work was performed in partial fulfillment of the degree of MSc in the Department of Physiology at Queen’s University in Kingston, Ontario, Canada (BNR).

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Roy, B.N., Van Vugt, D.A., Weagle, G.E. et al. Effect of 5-Aminolevulinic Acid Dose and Estrogen on Protoporphyrin IX Concentrations in the Rat Uterus. Reprod. Sci. 4, 40–46 (1997). https://doi.org/10.1016/S1071-5576(96)00062-7

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  • DOI: https://doi.org/10.1016/S1071-5576(96)00062-7

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