title: Prenatal exposure to integerrimine N-oxide impaired the maternal care and the physical and behavioral development of offspring rats.
abstract: Plants that contain pyrrolizidine alkaloids (PAs) have been reported as contaminants of pastures and food, as well as being used in herbal medicine. PAs are responsible for poisoning events in livestock and human beings. The aim of this present study was to evaluate effects of prenatal exposure to integerrimine N-oxide, the main PA found in the butanolic residue (BR) of Senecio brasiliensis, on both physical and behavioral parameters of Wistar rat offspring. The toxicity and maternal behavior were also evaluated. For this, pregnant Wistar rats received integerrimine N-oxide from the BR of Senecio brasiliensis, by gavage, on gestational days 6-20 (during organogenesis and fetal development period) at doses of 3, 6 and 9 mg/kg. During treatment, maternal body weight gain, and food and water intake were evaluated. After parturition, maternal behavior and aggressive maternal behavior were analyzed. In addition, physical development and behavioral assessments were observed in both male and female pups. Results showed that prenatal exposure to integerrimine N-oxide of S. brasiliensis induced maternal toxicity, impairment in maternal behavior and aggressive maternal behavior, mainly in the highest dose group. Between sexes comparison of pups showed loss of body weight, delayed physical development such as pinna detachment, hair growth, eruption of incisor teeth, eye and vaginal openings. These pups also showed a delay of palmar grasp, surface righting reflex, negative geotaxis and auditory startle reflexes. Thus, prenatal exposure to integerrimine N-oxide induces maternal toxicity, impairment of maternal care and delayed in physical and behavioral development of the offspring.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 580, 05508-000 São Paulo, Brazil. Electronic address: thaisasandini@usp.br.
authors.forename: Thaísa M
authors.initials: TM
authors.lastname: Sandini
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Dr. Lineu Prestes, 580, 05508-000 São Paulo, Brazil.
authors.forename: Mariana S B
authors.initials: MS
authors.lastname: Udo
authors.affiliation: Department of Neuroscience, Institute of Psychology, University of São Paulo, Av. Prof. Dr. Melo de Morais, 1721, 05508-030 São Paulo, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Reis-Silva
authors.affiliation: Graduate Program of Environmental and Experimental Pathology and Graduate Program Dentistry, Paulista University, UNIP, Rua Dr. Bacelar, 1212, 04026-002 São Paulo, Brazil.
authors.forename: Maria Martha
authors.initials: MM
authors.lastname: Bernardi
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of Sao Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, 05508 270 São Paulo, Brazil.
authors.forename: Helenice de S
authors.initials: Hde S
authors.lastname: Spinosa
mesh_terms: D000367:Age Factors; D000374:Aggression; D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002658:Developmental Disabilities / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000503:physiopathology*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D051381:Rats; D018709:Statistics, Nonparametric
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; C009237:senecionine
keywords: Behavior; Maternal care; Neurodevelopment; Offspring; Prenatal; Pyrrolizidine alkaloids