title: Effect of continuous and multiple doses of 5-aminolevulinic acid on protoporphyrin IX concentrations in the rat uterus.
abstract: The objective of the present study was to determine if the concentration of protoporphyrin IX (PpIX) in the rat endometrium could be increased by administering 5-aminolevulinic acid (ALA) in multiple doses or by continuous infusion. The effect of pH, temperature and time in solution on the stability of ALA were also investigated. Estrogen-filled silastic capsules were implanted subcutaneously into ovary intact female rats (200-225 g) (n = 66). On the third day of hormonal priming, ALA (10 mg or 25 mg) dissolved in saline and adjusted to a pH of 5-5.5 was administered intrauterine either as a single bolus or as two injections 3 hours apart (n = 10). A fifth group of rats was infused with 25 mg ALA over a 12 hour period using an osmotic minipump (n = 6). In a second experiment, ALA (25 mg) was injected immediately after being dissolved in saline (pH 2) (n = 16) or after incubation at 37 degrees C for 12 hour (pH 2) (n = 7). PpIX was then extracted from the endometrium and myometrium using a 1:1 methanol/perchloric acid solution and quantified spectrofluorometrically. A dose-response relationship was observed between 10 and 25 mg of ALA and endometrial PpIX concentrations. However, no differences in endometrial PpIX concentrations were detected between rats administered ALA either as a single bolus or as two doses. Continuous infusion of 25 mg of ALA resulted in statistically lower endometrial PpIX concentrations compared to 25 mg ALA injected either as a single bolus or as two injections. Neither pH, temperature, nor time in solution affected ALA-induced PpIX accumulation. We conclude that the simplest way of achieving the highest PpIX concentration in the rat endometrium in vivo is to administer a bolus injection of 25 mg of ALA.
authors.affiliation: Department of Physiology, Queen's University, Kingston, Ont., Canada.
authors.forename: B N
authors.initials: BN
authors.lastname: Roy
authors.forename: D A
authors.initials: DA
authors.lastname: Van Vugt
authors.forename: G E
authors.initials: GE
authors.lastname: Weagle
authors.forename: R H
authors.initials: RH
authors.lastname: Pottier
authors.forename: R L
authors.initials: RL
authors.lastname: Reid
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D011524:Protoporphyrins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013696:Temperature; D013997:Time Factors
chemical_list: D011524:Protoporphyrins; D012996:Solutions; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX