Shamapari R, Nagaraj K
Department of PG Studies and Research in Applied Zoology, Kuvempu University, Jnana Sahyadri, Shankaraghatta, Karnataka 577451, India.
Toxicol Res (Camb). 2024 Nov 5;13(6):tfae180. doi: 10.1093/toxres/tfae180. eCollection 2024 Dec.
Clobazam (CLB) and Vigabatrin (VGB) are commonly used antiepileptic drugs (AEDs) in the treatment of epilepsy. Here, we have examined the genotoxic effect of these AEDs in . The Drosophila larvae were exposed to different concentrations of CLB and VGB containing food media. The assessment encompassed oxidative stress, DNA damage, protein levels, and gene expression profiles. In the CLB-treated group, a reduction in reactive oxygen species (ROS) and lipid peroxidation (LPO) levels was observed, alongside increased levels of superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO). Conversely, the VGB-treated group displayed contrasting results, with increased ROS and LPO and decreased SOD, CAT, and NO levels. However, both CLB and VGB induced DNA damage in Drosophila. Proteomic analysis (SDS-PAGE and OHRLCMS) in the CLB and VGB groups identified numerous proteins, including Acyl-CoA synthetase long-chain, NADH-ubiquinone oxidoreductase 75 kDa subunit, V-type proton ATPase subunit E, ADP/ATP carrier protein, malic enzyme, and DNA-binding protein modulo. These proteins were found to be associated with pathways like growth promotion, notch signaling, Wnt signaling, neuromuscular junction (NMJ) signaling, bone morphogenetic protein (BMP) signaling, and other GABAergic mechanisms. Furthermore, mRNA levels of ACSL, ND75, Vha26, sesB, and Men genes were upregulated in both CLB and VGB-treated groups. These findings suggest that CLB and VGB could have the potential to induce genotoxicity and post-transcriptional modifications in humans, highlighting the importance of monitoring their effects when used as AEDs.
氯巴占（CLB）和氨己烯酸（VGB）是治疗癫痫常用的抗癫痫药物（AEDs）。在此，我们研究了这些AEDs在[具体内容缺失]中的遗传毒性作用。将果蝇幼虫暴露于含有不同浓度CLB和VGB的食物培养基中。评估包括氧化应激、DNA损伤、蛋白质水平和基因表达谱。在CLB处理组中，观察到活性氧（ROS）和脂质过氧化（LPO）水平降低，同时超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和一氧化氮（NO）水平升高。相反，VGB处理组显示出相反的结果，ROS和LPO增加，SOD、CAT和NO水平降低。然而，CLB和VGB均诱导果蝇DNA损伤。CLB组和VGB组的蛋白质组分析（SDS-PAGE和OHRLCMS）鉴定出许多蛋白质，包括酰基辅酶A合成酶长链、NADH-泛醌氧化还原酶75 kDa亚基、V型质子ATP酶亚基E、ADP/ATP载体蛋白、苹果酸酶和DNA结合蛋白模体。发现这些蛋白质与生长促进、Notch信号传导、Wnt信号传导、神经肌肉接头（NMJ）信号传导、骨形态发生蛋白（BMP）信号传导和其他GABA能机制等途径相关。此外，在CLB和VGB处理组中，ACSL、ND75、Vha26、sesB和Men基因的mRNA水平均上调。这些发现表明，CLB和VGB可能有潜力在人类中诱导遗传毒性和转录后修饰，突出了在将其用作AEDs时监测其作用的重要性。
