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| The psoralens are naturally occurring plant metabolites found in
common fruit and vegetable crops. Synthetic forms of 8-methoxypsoralen
(xanthotoxin or methoxsalen) and 5-methoxypsoralen (bergapten) are widely used
as drugs in skin photochemotherapy (PUVA) and have been used as tanning
activators in many sunscreen preparations. Unfortunately, PUVA has been shown
to have major side effects. For example, malignant melanoma. Induced abortions,
and spontaneous abortions have been reported in patients under PUVA. An
increase in low birthweight infants has also been reported. Recent studies have
shown that the psoralens have adverse reproductive effects in rats. Therefore,
these chemicals could also represent a risk for infertility or birth defects in
humans. |
 Dr. Moussa Diawara Entomology and Toxicology |
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 Comet
Assay result (click image for larger view) |
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The study
uses the following methodologies. Each psoralen will be administered orally or
by injection in male and female wistar rats during acute and subchronic tests.
Its effects will be observed in tissue culture and in vitro experiments. Its
impact on secretion of reproductive hormones, gene expression, and gonadal
function will also be determined.
The Specific Aims are to: I) investigate the direct effect of xanthotoxin or bergapten dosing
on the hypothalamo/pituitary axis in female and male rats, II) investigate the direct effect of xanthotoxin or bergapten dosing
on gonadal function in female and male rats, and III) investigate the role of
the male in xanthotoxin- or bergapten-induced pregnancy effects. |
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| The results of the proposed study will help a) establish the role of
the hypothalamo-pituitary-gonadal axis in the response of the reproductive
system to environmental insults such as the psoralens; b) provide dramatic
insight into the potential reproductive toxicity
of the psoralens in female and male reproductive systems; c) better understand
gender differences in the response of the male and female reproductive systems
to xenobiotic exposures; and d) reduce the risk in women and men who are
exposed to therapeutic (medicinal use), dietary (produce handling and/or
consumption), cosmetic (sunscreen use), or occupational (agricultural or
industrial work) psoralens.
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