Reproductive toxicity of the psoralens.
The psoralens are naturally occurring secondary metabolites in plants, including many fruits and vegetables. Health risks have been associated with handling or ingesting psoralen-containing plants, and with the use of synthetic psoralens in photochemotherapy of skin disorders. Our research has demonstrated that administration of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) in the diet of female rats reduced birthrates, number of implantation sites, pups, corpora lutea, full and empty uterine weight, and circulating estrogen levels in a dose-dependent manner. Psoralens induced mRNAs of the liver enzymes CYP1A1 and UGT1A6, suggesting that enhanced metabolism of estrogens by psoralen treatment may explain the reproductive toxicity and the observed reduction of ovarian follicular function and ovulation. Rats also avoided repeated consumption of a flavored solution associated with psoralen administration. The findings indicate that the psoralens constitute a novel group of ovarian toxicants. Further examination of the safety of their use in photochemotherapy and diet is warranted.
Departments of Biology and Psychology, University of Southern Colorado, Pueblo, Colorado 81001, USA. moussa@uscolo.edu
Moussa M
MM
Diawara
Paul J
PJ
Kulkosky
D000078223:5-Methoxypsoralen; D000284:Administration, Oral; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000097:blood; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008730:Methoxsalen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D009004:Monosaccharide Transport Proteins; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D000099237:UDP-Galactose Translocators
D000078223:5-Methoxypsoralen; D019363:Cytochrome P-450 CYP1A1; D004967:Estrogens; D014453:Glucuronosyltransferase; D008730:Methoxsalen; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D000099237:UDP-Galactose Translocators