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

Bowers, Miriam A.; Luckhurst, Cherie; Davis, Holly A.; Woods, James S.

doi:10.1016/0272-0590(92)90092-v

Cited by 7 publications

(4 citation statements)

References 13 publications

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“…The importance of renal function markers in a rat strain as an index of exposure was proposed by Bowers et al (1992). A consistently low urinary excretion rate of porphyrin was found in F344 rats, while in Sprague-Dawley animals this rate was considerably higher and variable.…”

Section: Kidneymentioning

confidence: 98%

Editorial

Kacew

Festing²

1996

Journal of Toxicology and Environmental Health

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The development of drugs to combat diseases, chemicals to improve food production, or compounds to enhance the quality of life necessitates, by law, the use of laboratory animals to test their safety. In order to simulate the human condition it is necessary to choose a species in which pharmacokinetic and toxicokinetic mechanisms are established and resemble those of humans. The advantages of the use of the rat in drug and chemical toxicity testing include (a) metabolic pathway similarities to humans; (b) numerous similar anatomical and physiological characteristics; (c) a large database, which is extremely important for comparative purposes; and (d) the ease of breeding and maintenance of animals at relatively low cost. However, the choice of rat can be complicated, especially when over 200 different strains of rat are known to exist. The aim of this review is to summarize genetically determined differences in the responsiveness of rat strains to drugs and naturally occurring chemicals and to show that susceptibility is dependent on the target organ sensitivities, which may also be strain dependent. It is suggested that detailed studies of strain differences may help to clarify toxic mechanisms. Such studies are usually best conducted using inbred strains in which the genetic characteristics have been fixed, rather than in outbred stocks in which individual samples of animals may differ, the phenotype is variable, and the stocks are subject to substantial genetic drift. The fact that strains may differ also needs to be taken into account in assessing the potential hazard of the chemical, particularly when a study involves only a single strain and therefore provides no assessment of likely strain variation.

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Section: Kidneymentioning

confidence: 98%

Editorial

Kacew

Festing²

1996

Journal of Toxicology and Environmental Health

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“…Contains detailed information on HPLC analysis of human and rat urinary porphyrins and describes the effects of prolonged lead and mercury exposure on urinary porphyrin excretion. Bowers et al, 1992b. See above.…”

Section: Anticipated Resultsmentioning

confidence: 97%

“…Each porphyrin responds maximally at slightly different excitation and emission wavelengths. Excellent results have been obtained in terms of the detection of all extracted porphyrins in biological substances using an excitation wavelength in the range of 395 to 400 nm and an emission wavelength of 620 nm (Woods et al, ; Bowers et al, ; Woods and Miller, ). Spectrofluorometric analysis at these parameters permits the quantitative detection of 8‐ through 2‐carboxyl porphyrins, as well as for zinc protoporphyrin, with a sensitivity to detect 0.5 pmol in the column effluent.…”

Section: Commentarymentioning

confidence: 99%

HPLC Methods for Analysis of Porphyrins in Biological Media

Woods

Simmonds

2001

CP Toxicology

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“…85 Since that time, scores of scientific papers have been published describing the types of chemicals that can cause this type of acquired porphyria, including polychlorinated biphenyls, [86][87][88] polychlorinated dioxins, 89 and polychlorinated dibenzofurans. 90 These studies have been useful to delineate the effects of exacerbating factors (including sex, 91 strain differences, 91 iron levels, alcohol, and estrogens) on the time to onset and the degree to which porphyrins accumulate. In one of these studies, Cantoni et al found that UROD activity from a control mouse liver was markedly inhibited in vitro by the addition of cytosolic fractions from the livers of mice made porphyric by treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin, 89 but the chemical structure of this UROD inhibitor was not determined.…”

Section: Animal Models Of Pctmentioning

confidence: 99%

Genetic Aspects of Porphyria Cutanea Tarda

2007

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Porphyria cutanea tarda (PCT) is caused by disruption of heme biosynthesis at the step catalyzed by uroporphyrinogen decarboxylase. The patients present with photosensitive cutaneous lesions, hepatic pathology (including elevated porphyrin levels), and increased excretion of porphyrins. Therapy consists of removing the exacerbating factors of PCT (reduced sunlight exposure, abstinence from alcohol use, decreased estrogen exposure, and treatment for viral infections), decreasing body iron stores (by therapeutic phlebotomy or by the use of the new orally active iron chelators), and, in some instances, the use of low-dose antimalarials. Recent advances in genetics and genomics have allowed DNA testing for porphyria cutanea tarda and are likely to be instrumental in developing improved, gene-based treatments and in finding genetic loci (in addition to uroporphyrinogen decarboxylase) involved in the clinical expression of this disease.

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

Cited by 7 publications

References 13 publications

Editorial

Editorial

HPLC Methods for Analysis of Porphyrins in Biological Media

Genetic Aspects of Porphyria Cutanea Tarda

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