title: Neuro-immuno-teratogenicity of drugs used in neonatal pharmacotherapy in relation to the ontogenic stage at the time of their administration.
abstract: The risk of functional teratogenicity of two drugs used in neonatal pharmacotherapy was studied: indomethacin (INDO) and dexamethasone (DEX). Model experiments were carried out in Wistar strain rats, breed Konárovice, which received single subcutaneous drug injection (INDO 2 mg/kg, DEX 1 mg/kg) on postnatal day 4 (PD:4; model of human fetus/preterm newborn of 6-7-month-gestational age) or on postnatal day 9 (PD:9; model of full-term human neonate). The rats were followed up during development (body weight, maturation) till late adulthood (age 6-8 months) using tests of cognition, immune reactivity and biochemical brain analysis. The results evaluated by comparing treated and control litter-mates indicated that the functional teratogenic risk was significantly higher in DEX than in INDO. DEX-rats revealed disorganization of developmental processes: retardation of body growth, but acceleration of sensory development (pinna and eye opening), retarded male sexual maturation. Adult DEX-rats (age 6 months) of both series (PD:4, PD:9) had deficit of short-term memory (social recognition test). Disturbances of immune reactivity (decrease of humoral and rise of cell-mediated immune response) appeared both in adult INDO and DEX-rats (age 7 months), but only in the PD:9 series i.e. when the drugs were administered at a higher stage of the ontogenic development simulating neonatal period in humans. This finding may be warning from the clinical point of view for the neonatological practice.
authors.affiliation: Prague Psychiatric Center, Prague, Czech Republic. benesova@pcp.lf3.cuni.cz
authors.forename: O
authors.initials: O
authors.lastname: Benesová
authors.forename: H
authors.initials: H
authors.lastname: Tejkalová
authors.forename: Z
authors.initials: Z
authors.lastname: Kristofiková
authors.forename: V
authors.initials: V
authors.lastname: Panajotova
authors.forename: P
authors.initials: P
authors.lastname: Husek
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007213:Indomethacin / Q000633:toxicity*; D007231:Infant, Newborn; D008297:Male; D008568:Memory / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012919:Social Behavior; D013723:Teratogens / Q000633:toxicity*
chemical_list: D013723:Teratogens; D003907:Dexamethasone; D007213:Indomethacin