Resistance to Trichinella spiralis infection, induction of hepatic monooxygenases, and concentrations in thymus and liver in rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Abstract

Pregnant Wistar rats were treated on day 19 of gestation with a single s.c.-injection of 3 or 0.3 μg 2,3,7,8-tetrachlorodibenzo- p-dioxin (= TCDD)/kg body wt or with the vehicle only (toluene/DMSO, 1 + 2 v/v, 0.2 ml/kg body wt). The concentrations of TCDD in thymus and liver tissue as well as the activity of the ethoxyresorufin O-deethylase (EROD) in homogenate from maternal, fetal and offspring liver were determined up to 11 weeks postnatally (in the high dose group). Five weeks postnatally 12 male offspring were randomly selected from each of the control and of the two TCDD treated groups and infected orally with 500 Trichinella spiralis larvae. Two, three and six weeks after infection antibody titers to T. spiralis (IgM, IgG, IgE) were measured in the blood plasma. The weight of relevant organs was determined and the tongue was prepared for the counting of T. spiralis muscle larvae 11 weeks postnatally. EROD activity in maternal liver was increased 46-fold (648 pmol resorufin/mg x min) on day 22 of pregnancy (i.e. 3 days after treatment with TCDD) in comparison to untreated historical controls (14 ± 4 pmol resorufin/mg x min; n = 42). At this time point the highest TCDD concentration was measured in maternal liver (26.4 ng TCDD/g liver). A pronounced EROD induction was also demonstrable in fetal liver tissue (248 pmol resorufin/mg x min), however, the TCDD concentration in liver tissue was considerably lower (3.1 ng TCDD/g liver). In the offspring the highest EROD induction was observed on day 1 after birth (346 pmol resorufin/mg x min; TCDD concentration: 5.7 ng TCDD/g liver). One week after birth, highest concentrations were measured in the offspring liver (34 ng TCDD/g liver), but no corresponding increase in enzyme induction was seen (343 pmol resorufin/mg x min). Thereafter, TCDD concentrations as well as monooxygenase activity declined continuously in offspring and maternal liver tissue. A maximum concentration of 1.69 ng TCDD/g thymus tissue was measured on day 1 postnatally in maternal thymus. The peak concentration in the thymi of the offspring was measured one week after birth (0.67 ng TCDD/g). During the time period between four weeks and 11 weeks after birth TCDD concentrations in maternal and offspring thymi were determined between 0.11 and 0.18 ng TCDD/g wet weight, without showing a clear-cut decline. Eleven weeks postnatally the body weight was decreased significantly in the offspring of the high dose group and the mortality rate after infection with T. spiralis seemed to be increased in the 3 μg TCDD/kg body wt group. Relative weights of thymus and liver were significantly decreased after exposure to 0.3 μg TCDD/kg body wt. No significant differences were found in the antibody titers to T. spiralis (IgM, IgG, IgE) and the number of T. spiralis muscle larvae between the control and the TCDD treated groups of offspring. We conclude that the perinatal exposure of rat offspring to TCDD under our experimental conditions led to a pronounced induction of hepatic monooxygenases but did not impair the immune system in such a way that it was clearly detectable with the T. spiralis infectivity model.