AI Article Synopsis
- The study investigates the effects of prenatal exposure to integerrimine N-oxide, a toxic compound found in the plant Senecio brasiliensis, on Wistar rat offspring.
- Pregnant rats were given varying doses of the compound during key developmental days, and researchers monitored maternal health and behavior, as well as the physical and behavioral development of the pups.
- Results indicated that high doses led to maternal toxicity, reduced maternal care, and significant delays in the growth and development of the offspring.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijdevneu.2014.05.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Indirect photodegradation of typical pyrrolizidine alkaloids in water induced by triplet states of dissolved organic matter.
J Hazard Mater
September 2024
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China.
The occurrence of pyrrolizidine alkaloids (PAs) in the aquatic environment has received growing attention due to their persistent mutagenicity and carcinogenicity. In this study, the photooxidation processes of four representative PAs (senecionine, senecionine N-oxide, europine, and heliotrine) in the presence of dissolved organic matter (DOM) were investigated. The excited triplet DOM (DOM*) was demonstrated to play a dominant role in the phototransformation of PAs.
View Article and Find Full Text PDFVacuum differential mobility spectrometry combined with column-switching liquid chromatography- mass spectrometry for the analysis of pyrrolizidine alkaloids in tea samples.
J Chromatogr A
August 2023
Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland. Electronic address:
The benefit of combining liquid chromatography (LC), supercritical fluid chromatography (SFC) and vacuum Differential Mobility Spectrometry - Mass Spectrometry (vDMS-MS) was investigated for the analysis of fourteen diastereomeric pyrrolizidine alkaloids (PA); intermedine, echinatine, lycopsamine, indicine, intermedine-N-oxide, echinatine-N-oxide, indicine-N-oxide, lycopsamine-N-oxide, senecivernine, senecionine, jacobine, senecivernine-N-oxide, senecionine-N-oxide, retrorsine. The mobile phase composition (15-100% MeOH and ACN), flow rate (8-100 µL/min), vDMS cell pressure, and F value showed an effect on the mobility behavior of the analytes. At 15% MeOH with a flow rate of 100 µL/min and 33 mbar vDMS pressure, 8 out 14 PA could be partially or totally separated by vDMS-MS.
View Article and Find Full Text PDFSpecies difference in toxicokinetics and safety assessment of senecionine N-oxide in a UDP-glucuronosyltransferase 1A4 humanized mouse model.
Chem Biol Interact
August 2023
The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China; Shanghai R & D Center for Standardization of Traditional Chinese Medicines, Shanghai, 201210, China. Electronic address:
Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins, and herbs containing PAs are of high concern. PAs are normally found in tertiary amines and N-oxide forms (PA N-oxides), yet the latter are less evaluated for their toxicokinetics. As a continuation of our investigation into the safety assessment of PA-containing herbal medicines, the toxicity and toxicokinetic characteristics of senecionine N-oxide (a representative toxic PA N-oxide) were investigated by using the UDP-glucuronosyltransferase 1A4 humanized mouse model (hUGT1A4 mouse model) and compared with those in wild-type mice simultaneously.
View Article and Find Full Text PDFPhysiologically based kinetic modeling of senecionine N-oxide in rats as a new approach methodology to define the effects of dose and endpoint used on relative potency values of pyrrolizidine alkaloid N-oxides.
Front Pharmacol
March 2023
Division of Toxicology, Wageningen University, Wageningen, Netherlands.
Over 1,000 pyrrolizidine alkaloids (PAs) and their N-oxides (PA-N-oxides) occur in 3% of all flowering plants. PA-N-oxides are toxic when reduced to their parent PAs, which are bioactivated into pyrrole intermediates that generate protein- and DNA-adducts resulting in liver toxicity and carcinogenicity. Literature data for senecionine N-oxide in rats indicate that the relative potency (REP) value of this PA-N-oxide compared to its parent PA senecionine varies with the endpoint used.
View Article and Find Full Text PDFPhysiologically-Based Kinetic Modeling Predicts Similar In Vivo Relative Potency of Senecionine N-Oxide for Rat and Human at Realistic Low Exposure Levels.
Mol Nutr Food Res
February 2023
Division of Toxicology, Wageningen University, PO Box 8000, Wageningen, 6700 EA, The Netherlands.
Scope: This study aims to determine if previously developed physiologically-based kinetic (PBK) model in rat can be modified for senecionine (SEN) and its N-oxide (SENO), and be used to investigate potential species differences between rat and human in relative potency (REP) of the N-oxide relative to the parent pyrrolizidine alkaloid (PA).
Methods And Results: In vitro derived kinetic parameters including the apparent maximum velocities (V ) and Michaelis-Menten constants (K ) for SENO reduction and SEN clearance are used to define the PBK models. The rat model is validated with published animal data, and the toxicokinetic profiles of SEN from either orally-administered SENO or SEN are simulated.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!