The psoralens adversely affect reproductive function in male wistar rats.

The psoralens occur naturally in produce and are widely used in skin therapy. Studies show that 5-methoxypsoralen and 8-methoxypsoralen reduced birth rates in rats. We determined the effect of psoralens on reproductive function in male rats. Male Wistar rats were dosed daily with 5-methoxypsoralen or 8-methoxypsoralen (75 or 150 mg/kg, p.o.), or vehicle control. Treated males had significantly smaller pituitary glands, fewer sperm per ejaculate, and fewer sperm in the vasa defferentia and epididymides than controls. Dosing significantly elevated levels of testosterone and increased relative testis weight, but did not directly affect testicular weight. Females bred to dosed males required more time to become pregnant, and these males required more breeding attempts. The findings demonstrate the importance of determining the potential risk for infertility and/or birth defects in humans who are exposed to therapeutic, dietary, or occupational psoralens.

Examination of psoralens-induced photodermatitis in Wistar rats under scanning electron microscopy.

The psoralens are photoactivated plant biosynthetic compounds which are found in several plant families, including common fruits and vegetables. Synthetic forms of the psoralens bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen) are extensively used in skin chemotherapy in combination with long-wave ultraviolet radiation (PUVA). Side effects of PUVA therapy are not, however, desirable, and this therapy has been linked with increased incidence of skin cancer in humans. The psoralens are known to be carcinogenic, mutagenic and teratogenic, and to cause photodermatitis. The main objective of this study was to document the effect of PUVA on the epidermis of rats. Female Wistar rats were administered dietary bergapten and/or xanthotoxin (0-200 mg/kg body) and exposed to UVA radiation (45 min./day) for four weeks. At the end of the four-week period the rats were sacrificed; skin samples were taken from the ears and the top part of the tail and fixed for examination by Scanning Electron Microscopy. The animals subjected to PUVA had significantly smaller scales on the tail epidermis (mean scale size for the control 926 mu vs. 725 to 805 mu for the psoralen treatment groups. The rats that received dietary psoralens also had significantly less hair on the ears compared with the control animals (mean number of hairs per millimeter over the ear edge for the control 54.9 vs. 2.00 to 10.7 for the treatment groups). The two compounds were synergistic in their ability to reduce scale size on the tail epidermis.

A novel group of ovarian toxicants: the psoralens.

The psoralens are naturally occurring metabolites found in many crop plants; synthetic forms of 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxin) are widely used in skin photochemotherapy. Our previous research documented that dietary bergapten and xanthotoxin reduced birthrates in female rats when males and females were exposed to these chemicals. The present study was designed to determine the cause of this reduced birthrate and whether this resulted from direct impact on the females. The study demonstrates that bergapten and xanthotoxin administered, either alone or in combination to female rats (mated to undosed males), significantly reduced the number of implantation sites, pups, and corpora lutea in dosed females compared with control animals. Additionally, full uterine weight and empty uterine weight were significantly reduced. These compounds also significantly reduced circulating estrogen levels in a dose-dependent manner. Interestingly, the psoralens significantly induced mRNAs of liver enzymes typically induced by polycyclic aromatic hydrocarbons, CYP1A1 and UGT1A6; the higher the dose, the greater the induction. UGT 2B1 mRNA, typically induced by phenobarbital-like compounds, was not significantly affected. Thus, enhanced oxidative metabolism and conjugation of estrogens in psoralen-treated animals may provide a partial explanation for the effects observed. These findings are also consistent with psoralen-induced reduction in ovarian follicular function and ovulation.