title: Prenatal exposure to integerrimine N-oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood.
abstract: Pyrrolizidine alkaloids (PAs) are toxins that are exclusively biosynthesized by plants and are commonly present in foods and herbs. PAs are usually associated with poisoning events in livestock and human beings. The aim of the present study was to evaluate the behavioral and neurochemical effects of prenatal exposure to PA integerrimine N-oxide of rats in adulthood. Pregnant Wistar rats received integerrimine N-oxide from the butanolic residue of Senecio brasiliensis by gavage on gestational days 6-20 at doses of 3, 6 and 9 mg/kg. During adulthood of the offspring, the following behavioral tests were performed: open-field, plus-maze, forced swimming, catalepsy and stereotypy. Histological analyses and monoamine levels were measured. Male offspring from dams that were exposed to 9 mg/kg showed an increase in locomotion in the open-field test, an increased frequency of entries and time spent in open arms in elevated plus-maze test, as well as decreased swimming time. In the female offspring from dams that were exposed to 9 mg/kg, there was an increased time of climbing in forced swimming and intensity of stereotyped behavior. The histological study indicates an increase in the number of multinucleated cells in the liver (6 and 9 mg/kg). In neurotransmitter analysis, specifically in the striatum, we observed change in dopamine and serotonin levels in the middle dose. Thus, our results indicate that prenatal exposure to integerrimine N-oxide changed behavior in adulthood and neurotransmitter levels in the striatum. Our results agree with previous studies, which showed that integerrimine N-oxide impaired physical and neurobehavioral development in childhood that can persist until adulthood.
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: 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: Daniel
authors.initials: D
authors.lastname: Sanches
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: Jorge Camilo
authors.initials: JC
authors.lastname: Flório
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; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013239:Stereotyped Behavior / Q000187:drug effects; D013550:Swimming / Q000523:psychology; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D018377:Neurotransmitter Agents; D011763:Pyrrolizidine Alkaloids; C009237:senecionine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Neurobehavioral; Offspring; Pyrrolizidine alkaloids; Rats; Senecio