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.

Prenatal exposure to integerrimine N‐oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood

“…Open‐field testing is commonly used to measure behavioral responses, such as locomotor activity (Patti et al, 2005), hyperactivity (Fukushiro et al, 2008), exploratory behavior and anxiety (Prut and Belzung, 2003). In our previous study, no alterations in open‐field behavior during infancy were observed (Sandini et al, 2014). However, in the present study, we observed that male rats that were treated prenatally with 9 mg/kg integerrimine N‐oxide showed increased locomotion in adulthood.…”

“…PAs are generally hepatotoxic, and there is some evidence that integerrimine N‐oxide can cause neurotoxic effects in vivo (Gimmeler, 1986; Sandini et al, 2014). Thus, we investigated possible alterations in the central nervous system in rats during adulthood because our previous studies showed that this treatment can cause alterations in maternal behavior and impair the physical development of offspring (Sandini et al, 2014).…”

“…The experiment was performed as previously described (Sandini et al, 2014). Briefly, this experiment consists of a round 96‐cm‐diameter arena that is surrounded by a 25‐cm‐high enclosure that was painted white and subdivided into 25 black‐lined areas.…”

“…On PND2, all of the litters were examined externally and sexed. Reproductive parameters and physical and neurodevelopmental evaluations on these same offspring were reported in a previous publication (Sandini et al, 2014). The pups were weaned at PND21 when the offspring were separated by sex and treatment groups and maintained under identical conditions as their dams until adulthood (PND75).…”

“…However, the literature has little information regarding the toxic effects of PAs on postnatal development in animal models. Previously, we have observed that the treatment of dams with integerrimine N‐oxide (PA) during gestation caused impairment in physical and behavioral development in pups at the infancy (Sandini et al, 2014). These alterations during development could have long‐term effects on the pups' central nervous function.…”