Effects of lincomycin hydrochloride on the neurotoxicity of zebrafish.

Lincomycin hydrochloride is one of the commonly used drugs in clinic. However, it has many side effects on patients, and its mechanism is still poorly understood. In this study, 6 h post-fertilization (6 hpf) zebrafish embryos were exposed to several concentrations of lincomycin hydrochloride (15, 30, 60 µg/mL) for up to 24 or 96 hpf to detect their developmental toxicity and neurotoxicity, and to 6 days post-fertilization (6 dpf) to detect their behavioral toxicity. Our results showed that lincomycin hydrochloride could lead to embryonic head deformities (unclear ventricles, smaller ventricles, fewer new neurons). The studies showed that the frequency of spontaneous tail flick of zebrafish embryo increased at 24 hpf, and the lincomycin hydrochloride exposed zebrafish embryos showed increased heart rate, shorter body length, and yolk sac edema with severe pericardial edema at 96 hpf. The studies also showed that lincomycin hydrochloride increased oxidative stress level, Acetylcholinesterase (AChE) activity, ATPase activity and apoptosis in zebrafish larvae. In addition, the swimming behavior of zebrafish larvae decreased with the increase of lincomycin hydrochloride concentration, but the angular velocity and meandering degree increased, which might be due to the decreased activity of AChE and ATPase, as well as the decreased expression of genes related to neurodevelopment and neurotransmitter system, leading to the change of their motor behaviors. In summary, we found that lincomycin hydrochloride induced developmental toxicity and neurotoxicity in zebrafish larvae, contributing to a more comprehensive evaluation of the safety of the drug.

Prenatal exposure to selective serotonin reuptake inhibitors and infant outcome.

BACKGROUND: The selective serotonin reuptake inhibitors are prescribed increasingly also during pregnancy. Although a number of studies have assessed their safety, data concerning congenital malformations and adverse perinatal outcome are conflicting. METHODS: Literature search in PubMed until March 31, 2012, including original research articles, meta-analyses, and reviews. RESULTS: Fluoxetine and paroxetine use in early pregnancy has been associated with a small increased risk for specific cardiovascular malformations in some studies, fluoxetine with ventricular septal defects and paroxetine with right ventricular outflow tract defects. The observed absolute risk for these specific malformations is small. Data on preterm birth, low birth weight, and being small for gestational age have been conflicting; and mother's underlying depression is obviously an important confounder. Respiratory distress and neonatal adaptation problems are common in prenatally exposed infants, and an increased risk for persistent pulmonary hypertension of the newborn has been observed in several studies. Although several studies have not confirmed an increased risk for adverse neurodevelopment, a recent study observed an increased risk for autism spectrum disorders in prenatally exposed offspring. CONCLUSIONS: Causality cannot be confirmed in observational study settings. However, parallel results in individual studies regarding the cardiac malformations and pulmonary hypertension of the newborn, together with an existing biologically plausible mechanism behind these events may support causality. Considering the important role of serotonin in central nervous system development, more studies are needed to assess the possible adverse effects on long-term neurodevelopment.