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However, alternative testing methods are being developed in an attempt to minimize mammalian testing while still retaining the integrity of toxicity testing of new industrial chemicals and medications. The ability of the zebrafish embryo to distinguish between valproic acid and 14 analogues was investigated by exposing zebrafish embryos for 120 h post fertilization in the extended version of the fish embryo acute toxic toxicity test, as well as analyzing liver histology to determine the relationship between liver function and the molecular structure of each compound. Although histological analysis of zebrafish liver did not reveal steatosis as the most common adverse effect present in human and mice, the structure-activity relationship derived was not limited to human HepG2 cells but also to rodent and rat data. Consequently, there is evidence that zebrafish embryos can be used as a bridge between subcellular, cell-based designs and vertebrate models.
Source link: https://doi.org/10.1007/s00204-022-03340-z
Autism spectrum disorder is a neurodevelopmental disorder characterized by key signs, including impairments in social functioning and repetitive interests. According to another study, people with ASD have decreased empathy, triggering social difficulties; however, people with ASD have increased emotional intelligence; however, another study found that people with ASD have increased emotional intelligence. However, the underlying neurobiological mechanisms underlying increased empathy in people with ASD remain unclear. We reviewed empathy-like behaviors in valproic acid-treated mice-a mouse model of ASD with observational fear learning in this research. After observational anxiety learning, a new number of c-Fos positive oxytocinergic neurons in the hypothalamus's paraventricular nucleus was significantly higher in VPA-treated mice. For the first time, these results show that VPA-treated ASD model animals displayed increased emotional empathy-like behaviours as a result of the hyperactivation of PVN oxytocinergic neurons.
Source link: https://doi.org/10.1248/bpb.b22-00200
Valproic acid is a multi-target drug commonly used to treat epilepsy. This study, however, we found the effect of prenatal exposure to VPA on microglial numbers during early postnatal brain development in a cohort. In male mice, prenatal exposure to VPA leads to a dramatic decrease in the number of microglia in the primary motor cortex during early postnatal brain growth, particularly at postnatal day 6 and postnatal day 10. Early microglial decline in the VPA model coincides with rapid cortical syntegenesis and is significant because it may have a role in mediating ASD's poor connectivity.
Source link: https://doi.org/10.3390/toxics10070379
For augmentation therapy in treatment-resistant schizophrenia, the combination of valproic acid and clozapine is often used for augmentation therapy. The aim of this research is to investigate the differences between patients treated with CLZ and patients treated with CLZ plus VPA. The study was based on plasma samples from CLZ and CLZ plus VPA treated patients undergoing regular therapeutic drug testing, including clinical data, smoking status, daily dose of CLZ and VPA, concomitant medications, albumin, and renal and hepatic function. Plasma CLZ and NCLZ concentrations were determined by Liquid Chromatography-Tandem masses and plasma VPA by Ultraviolet-Visible spectrophotometric immunoassay. Patients with UGT2B10 GG genotype had lower NCLZ plasma and C/D NCLZ, as well as a higher CLZ/NCLZ ratio compared to patients with UGT2B10 GG genotype.
Source link: https://doi.org/10.1016/j.cbi.2022.110042
Autism spectrum disorder is a developmental disorder characterized by sensory abnormalities, social skills impairment, and cognitive deficits. Although new data showed that induction of autism-like behaviour in animal models leads to abnormal neuronal excitability, autism-like behavior in animal models is also a topic. Findings revealed that VPA exposure caused a significant rise in the hot plate reaction latency. neurons from VPA-exposed rabbits exhibited altered excitability characteristics in reaction to depolarizing current injections relative to control neurons, as well as these behavioral changes. In the hippocampal CA1 region of the VPA-exposed rats, the changes in the evoked electrophysiological characteristics were accompanied by intrinsic hyperexciteability and lower spike-frequency tolerance, as well as a significant rise in the number of NADPH-diaphorase stained neurons. In a rat model of autism-like, abnormal nociception and recognition memory is linked to changes in the neuronal responseness and nitrergic system.
Source link: https://doi.org/10.1016/j.brainres.2022.148013
In this research, 32 male Sprague-Dawley rats were used in total to investigate the effects of valproic acid on rat cerebellum. The experimental group was found to have valproic acid on embryonic day 15 and postnatal day 11, on the other hand, the control group was treated with saline on the same days. In addition, the granule cells had a smaller mean nuclear diameter in one of the experimental groups, while the Purkinje cells had smaller mean nuclear diameter in one of the experimental groups than those in the comparison group.
Source link: https://doi.org/10.1002/jdn.10213
Boron neutron capture therapy is a radiotherapeutic therapy that can kill cancer cells while sparing the surrounding normal cells. In this research, we wanted to determine whether VPA could have an increased effect in killing melanoma cells in conjunction with BNCT and discover the actual mechanism of VPA-BNCT's action in killing these cells.
Source link: https://doi.org/10.21873/anticanres.15828
We investigated how valproic acid interferes with PAHs' carcinogenesis in this study by altering macrophage function. We found that VPA promotes macrophage polarization in the tumor tissues, leading to the production of pro-inflammatory cytokines such as IFN-u03b3, IL-12, and TNF-u03b1, which in turn promotes tumor cell proliferation and tumor cell viability in tissue stroma of tumor cells. VPA can also influence the polarization of macrophages to influence cell growth of vascular endothelial cells by simulating tumor and normal cells on a cellular level.
Source link: https://doi.org/10.1016/j.ecoenv.2022.113779
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