Department of Chemistry, Faculty of Science, Yuzuncu Yıl University, Van, Turkey.
Department of Aquaculture, Faculty of Fisheries, Ataturk University, Erzurum, Turkey.
J Trace Elem Med Biol. 2022 Jul;72:126996. doi: 10.1016/j.jtemb.2022.126996. Epub 2022 May 11.
In recent years, therapeutic targets and the development of new drugs have shifted research towards inflammatory and oxidative stress pathways. Ferrocene (FcH) is a stable, small molecule that exhibits immunostimulatory and anti-tumor properties by a different mechanism and is effective at low doses in oral administration. However, it was surprising that there has been no performed investigation using FcH on aquaculture. On the other hand, recent papers reveal the key biological functions and health benefits due to daily boron intake in animals and humans. Therefore, we investigated the neurotoxic damage potential of FcH and its related neurotoxicity action mechanism in aquatic environments. In addition, the protective potential of borax (BX, or sodium borate) were evaluated againt in vivo neurotoxicity by FcH.
Neurotoxicity assessment was performed in rainbow trout brain tissue, acutely under semi-static conditions via determining a vide range of parameters including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities as well as glutathione (GSH), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA levels), DNA damage (8-OHdG), apoptosis (caspase 3), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), nuclear factor erythroid-2 (Nrf-2), acetylcholinesterase (AChE) and brain-derived neurotrophic factor (BDNF) levels. In addition, the LC 96 h level of FcH was determined for the first time in rainbow trout in this study.
In the obtained results, while FcH caused inhibition in enzyme activities, it showed an inducing effect on MDA, MPO, BDNF, Nrf2, TNF-α and IL-6 levels. It was determined that this oxidative damage related alterations were significantly different (p < 0.05) in comparison between FcH treated and controls. Again, the LC 96 h value in rainbow trout was determined as 11.73 mg/L, which is approximately 5% less than the value given for freshwater fish (12.3 mg/L). On the contrary, it was observed that BX has a mitigating effect on FcH-induced neurotoxicity.
The present study suggests that borax may be useful for preventing or alleviating neurotoxicity induced by environmental contaminants or toxic chemicals.
近年来,治疗靶点和新药的开发已将研究方向转向炎症和氧化应激途径。二茂铁(FcH)是一种稳定的小分子,通过不同的机制表现出免疫刺激和抗肿瘤特性,并且在低剂量口服时有效。然而,令人惊讶的是,在水产养殖中没有对 FcH 进行过研究。另一方面,最近的论文揭示了由于动物和人类日常硼摄入而导致的关键生物学功能和健康益处。因此,我们研究了 FcH 在水生环境中的神经毒性损伤潜力及其相关的神经毒性作用机制。此外,还评估了硼砂(BX,或硼酸钠)对 FcH 体内神经毒性的保护潜力。
通过在半静态条件下急性测定一系列参数,包括过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)活性以及谷胱甘肽(GSH)、髓过氧化物酶(MPO)、谷胱甘肽(GSH)、丙二醛(MDA)水平、DNA 损伤(8-OHdG)、凋亡(caspase 3)、肿瘤坏死因子-α(TNF-α)、白细胞介素 6(IL-6)、核因子红细胞 2(Nrf-2)、乙酰胆碱酯酶(AChE)和脑源性神经营养因子(BDNF)水平,在虹鳟鱼脑组织中进行神经毒性评估。此外,本研究首次在虹鳟鱼中确定了 FcH 的 96 小时 LC 值。
在获得的结果中,虽然 FcH 导致酶活性抑制,但它对 MDA、MPO、BDNF、Nrf2、TNF-α和 IL-6 水平表现出诱导作用。与对照组相比,这种与氧化损伤相关的变化在 FcH 处理组和对照组之间存在显著差异(p<0.05)。同样,在虹鳟鱼中确定的 96 小时 LC 值为 11.73mg/L,比淡水鱼类(12.3mg/L)给出的值低约 5%。相反,观察到 BX 对 FcH 诱导的神经毒性具有缓解作用。
本研究表明,硼砂可能有助于预防或减轻环境污染物或有毒化学物质引起的神经毒性。