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Effects of cyclosporin A and cyclophosphamide on Peyer's patches in rat, exposed in utero and neonatally or during adult age

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Author: Kuper, C.F. · Zijverden, M. van · Klaassen, C. · Tegelenbosch-Schouten, M. · Wolterbeek, A.P.M.
Institution: TNO Kwaliteit van Leven
Source:Toxicologic Pathology, 2, 35, 226-232
Identifier: 239896
doi: doi:10.1080/01926230601156245
Keywords: Biology · Toxicology and Applied Pharmacology · Adult exposure · Cyclophosphamide · Cyclosporin · Fetal exposure · Peyer's patches · Rat · cyclophosphamide · cyclosporin A · animal experiment · animal tissue · article · controlled study · drug effect · female · fetotoxicity · germinal center · gestation period · immunotoxicity · lactation · lymphocyte · male · microscopy · newborn period · nonhuman · Peyer patch · pregnancy · priority journal · rat · small intestine · Wistar rat · Administration, Oral · Aging · Animals · Cell Count · Cyclophosphamide · Cyclosporine · Female · Germinal Center · Immunosuppressive Agents · Injections, Intravenous · Male · Peyer's Patches · Pregnancy · Prenatal Exposure Delayed Effects · Rats · Rats, Wistar · Animalia · Rattus · Rattus norvegicus


The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats received orally 5 or 20 mg/kg/day CY or 5 or 10 mg/kg bw CPS for 4 weeks; males received orally 5 mg/kg bw CPS for 4 weeks, or a single iv injection of 50 mg/kg bw CPS. Upon in utero and neonatal exposure, the numbers of grossly observed PP were increased in male pups from the high-dose CY dams at 70 days of age. Exposure to high-dose CY at adult age only tended to decrease the numbers of PP; germinal center development was reduced in the PP from the middle segment of the small intestines, as examined microscopically. Exposure to both doses CPS at adult age reduced the numbers of PP and reduced germinal centre development and the number of lymphocytes in all compartments of PP. It was concluded that the effects of CPS and CY could be established by counting the number of grossly visible PP and by microscopic observation of PP, provided that regional differences of PP were taken into account. Moreover, the type of effects of an immunotoxic agent may vary with age of exposure. Copyright © by the Society of Toxicologic Pathology.