Investigation of factors influencing urinary porphyrin excretion in rats: Strain, gender, and age

Abstract

Urinary porphyrin excretion rates were evaluated in male rats of the Sprague-Dawley, Fischer 344, and Osborne-Mendel strains, and in female Fischer 344 rats, in order to identify an appropriate rat model for long-term studies of chemical-induced porphyria. Sprague-Dawley rats displayed a wide interanimal range in total 24-hr porphyrin excretion rates, from 0.9 to 59.6 nmol/24 hr (64-fold). Additionally, individual Sprague-Dawley rats varied by up to 5-fold in total porphyrins excreted from week to week over a 4-week period. Osborne-Mendel rats displayed a 12-fold interanimal difference in 24-hr total porphyrin excretion rates (ranging from 6.2 to 71.1 nmol/24 hr) and up to 4-fold individual variation from 1 week to another. In contrast, rats of the Fischer 344 strain displayed no significant differences in porphyrin excretion rates either among different animals or for individuals from week to week. Determination of individual porphyrin concentrations in the urine demonstrated that inconsistencies in total porphyrin concentration were attributable principally to differences in coproporphyrin concentrations. Frequency analysis of 24-hr coproporphyrin excretion levels among Sprague-Dawley rats demonstrated a widespread range encompassing low levels comparable to those of Fischer rats, high levels similar to those of most Osborne-Mendel rats, as well as intermediate levels. The mean total porphyrin excretion rate among female Fischer 344 rats was 1.2 ± 0.51 nmol/24 hr, compared to 2.1 ± 0.50 nmol/24 hr among male Fischer rats. Maturation and aging were found to have little influence on porphyrin excretion rates in male Fischer 344 rats. Among the three strains examined, the Fischer 344 strain appears most suitable for prolonged porphyrin evaluation studies by virtue of lower and more consistent basal porphyrin excretion rates among individuals of this strain.