Silymarin administration during pregnancy and breastfeeding: evaluation of initial development and adult behavior of mice

• Published in: Neurotoxicology (Park Forest South) 2020-05, Vol.78, p.64-70
• Main Authors: Barbosa, Caio Cesar, Nishimura, Akemy Nogueira, Santos, Monaliza Lopes dos, Junior, Walter Dias, Andersen, Monica Levy, Mazaro-Costa, Renata
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Behavior, Animal - drug effects; Body mass; Body Weight - drug effects; Breast feeding; Breastfeeding & lactation; Development; Euthanasia; Female; Genetic crosses; Gestation; Lactation; Male; Maternal Behavior - drug effects; Mice; Offspring; Phytotherapic safety; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - physiopathology; Prenatal Exposure Delayed Effects - psychology; Reproductive toxicology; Sensory evaluation; Sensory-Motor; Silybummarianum; Silymarin; Silymarin - toxicity; Vegetable oils
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2020.02.008

•Silymarin treatment has no effect on the course of pregnancy.•The treatment has no effect on the somatic development of the pups.•Maternal treatment has no effect on the cognition of adult pups.•Long-term treatment with silymarin not produced any significant effect on offspring. Silymarin is a phytotherapeutic agent derived from the species Silybum marianum (Asteraceae), commonly is known as milk thistle, and traditionally used as a hepatoprotective; however, recent studies have proposed its use in order to promote lactogenesis, but there are few reports of its effects on the development of offspring. Thus, the objective of this study was to evaluate the effect of silymarin treatment during pregnancy and breastfeeding on the sensory-somatic-motor development and adult behavior of F1-generation Swiss mice. The pregnant females of the parental generation were distributed in four experimental groups and treated orally with doses of 100, 200 or 300 mg/kg of silymarin, with a control group receiving vehicle – vegetable oil (VEH), to obtain the F1-generation. At the end of lactation, the parental generation were submitted to euthanasia. Body mass evolution was determined in both generations. The sensory-motor development of the offspring (F1-generation) was evaluated, and one male pup from each litter was followed up for an analysis of adult behavior. In the F1 analysis, no differences between the groups were observed in initial development from the sensory-somatic-motor analysis performed during the 1st to 21st postnatal days. In the behavioral evaluation of adults from the F1 generation, all the groups from dams treated with silymarin in open field (OF) analysis showed a decrease in the time spent in the periphery and an increase in the time spent in the center, but the ambulation observed by the number of quadrant crossed showed no difference. In addition, during OF, the 100 and 200 mg/kg groups presented an increase in fecal bolus compared with the VEH group. There was a decrease in immobility time in the forced swimming test in the 300 mg/kg group compared to the VEH group. Regarding the memory and learning test, the groups did not differ in their recognition scores. The results of this study using an animal model indicate that treatment with silymarin during pregnancy and breastfeeding does not promote significant morpho-functional changes in the offspring in their initial development and adult behavior, indicating the safety of its use during gestation a