Toxicological assessment and developmental abnormalities induced by butylparaben and ethylparaben exposure in zebrafish early-life stages.

Toxicological effects of butylparaben (BuP) and ethylparaben (EtP) on zebrafish (Danio rerio) early-life stages are not well established. The present study evaluated, using zebrafish embryos and larvae, the toxicity of BuP and EtP through benchmark dose (BMD) approach. BuP was more toxic than EtP to zebrafish larvae. In fact, Lethal Concentration 50 (LC50) values at 96 h post-fertilization (hpf) for BuP and EtP were 2.34 mg/L and 20.86 mg/L, respectively. Indeed, BMD confidence interval (lower bound (BMDL) - upper bound (BMDU) was 0.91-1.92 mg/L for BuP and 10.8-17.4 mg/L for EtP. Zebrafish embryos exposed to 1 mg/L, 2.5 mg/L of BuP and 5 mg/L, 10 mg/L, 20 mg/L, 30 mg/L of EtP showed several developmental abnormalities and teratological effects compared to negative control. Exposed zebrafish developed reduced heartbeat, reduction in blood circulation, blood stasis, pericardial edema, deformed notochord and misshaped yolk sac. Embryos exposed to the highest concentrations of the chemicals (2.5 mg/L of BuP, 10 mg/L, 20 mg/L and 30 mg/L of EtP) showed the developmental abnormalities at 48 hpf while those treated with 1 mg/L of BuP and 10 mg/L of EtP reported behavioral changes at 72 hpf, including trembling of head, pectoral fins and spinal cord. This research identified the lethal and sublethal effects of BuP and EtP in zebrafish early-life stages and could be helpful to elucidate the developmental pathways of toxicity of parabens.

Behavioral effects of acetyl-l-carnitine in the male rat.

The behavioral activity of carnitine acetylate derivative, acetyl-l-carnitine has been studied in the male rat. Intraperitoneal (IP) injection of acetyl-l-carnitine was followed by an increase in ambulation and rearing items in the open field behavior. Both the number of conditioned avoidance response (CARs) and the percentage of learners in the acquisition of shuttle-box active avoidance behavior appeared to be increased by IP or intracerebroventricular (ICV) injection of the drug at different doses. Subchronic administration of the drug mimicked the effects found after acute injection. The number of CARs in the extinction of shuttle-box active avoidance behavior appeared to be increased after acute IP or ICV injection, and after subchronic administration of acetyl-l-carnitine. The retention of passive avoidance behavior was facilitated by IP injection of the substance. The behavioral effects of acetyl-l-carnitine may involve central mechanisms, e.g., cholinergic neurotransmission in the brain.

Behavioral effects of perinatal administration of antidepressant drugs in the rat.

The monoamine reuptake blockers, imipramine, desipramine, and chlorimipramine, and the monoamine-oxidase inhibitors, iproniazid and isocarboxazid, were administered to pregnant rats (acutely at day 15 of pregnancy, or subchronically from day 10 of pregnancy to the delivery) or to newborn pups (from day 1 to day 5 of life). Prenatal acute injection of the antidepressant drugs failed to modify the development of neonatal reflexes of the rat pups and their adult behavior. Prenatal subchronic administration of the antidepressant drugs was followed by an increase in the number of pups showing neonatal reflexes, but also by an inhibition of the open field behavior and the acquisition of active avoidance responses tested in adulthood. In this respect, monoamine-oxidase inhibitors appeared to be more potent than monoamine reuptake blockers. Furthermore, neonatal administration of all the antidepressant drugs caused an inhibition of the acquisition of active avoidance responses tested in adulthood, but only the monoamine-oxidase inhibitor, isocarboxazid, significantly inhibited also the open field behavior of adult rats. Neither prenatal nor neonatal administration of the antidepressant drugs affected sexual activity of adult rats. The present results suggest that only a prolonged treatment with antidepressant drugs can affect neonatal or adult behavior of the rat, probably through an interference with central monoamine neurotransmission.

Behavioral effects of arginine in male rats.

The effects of aminoacid arginine on conditioned and unconditioned behavior were studied in male rats. Arginine was administered orally at different dose levels. Both acute and subchronic (7 days) treatment schedule was performed. Exploratory behavior of the rats was studied in an open field. Acquisition of active avoidance behavior was studied in the shuttle-box test situation, and retention of passive avoidance reaction was studied in a step-through type of passive avoidance behavior. Acute administration of arginine failed to affect the acquisition and the retention of avoidance responses, and exploratory behavior of the rats. A 7-day treatment with the aminoacid caused an increase in ambulation of rats of Wistar strain, and a facilitation of acquisition and retention of avoidance responses in rats of CDR strain with poor learning capacity. It is possible that behavioral effects or arginine depend on its involvement in nucleic acid synthesis.

Behavioral effects of phosphatidylserine after perinatal administration in rats.

Behavioral effects of the acidic phospholipid phosphatidylserine (PS) were studied in rats after perinatal (prenatal or neonatal) administration. PS was administered to pregnant rats from day 5 of pregnancy. PS liposomes were also injected i.p. to offspring from postnatal days 1-5. PS-treated rats showed a more precocious onset of neonatal behaviors, and a significant improvement in acquiring avoidance responses when tested at 60 days of age. Behavioral effects of PS may be related to a possible influence on dendritic arborization during perinatal period.