Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Biol Trace Elem Res. 2012 Jun;146(3):402-9. doi: 10.1007/s12011-011-9263-y. Epub 2011 Nov 19.
Cadmium (Cd) is a toxic heavy metal commonly found in industrial workplaces, a food contaminant and a major constituent of cigarette smoke. Most of the organs are susceptible to Cd-induced toxicity, including brain. Postnuclear supernatant (PNS) has been accepted as an in vitro model for assessing xenobiotic induced toxicity. The goal of the present study was to validate PNS as an in vitro model for investigating the effect of Cd-induced neurotoxicity. Neurotoxic induction by Cd was established in a dose-dependent manner in PNS in vitro. Enzymatic and non-enzymatic antioxidants were used as biomarkers of exposure. Antioxidant enzymatic activity was measured as a significant increase in activities of catalase, superoxide dismutase, and glutathione S-transferase. On exposure to Cd, a significant increase in acetylcholinesterase and decrease in sodium-potassium ATPase activity was also observed. Non-enzymatic effect was also demonstrated as a significant elevation in reduced glutathione and non-protein thiol activity, but there was no significant increase or decrease in the concentrations of protein thiol. In accordance with the toxicity of Cd towards the studied brain structure, Cd-induced oxidative stress has been a focus of toxicological research as a possible mechanism of neurotoxicity. Our results suggest that PNS preparations can be used as a model for future investigation of xenobiotic-induced neurotoxicity under in vitro conditions.
镉(Cd)是一种常见的工业工作场所中的有毒重金属,也是食物污染物和香烟烟雾的主要成分。大多数器官都容易受到镉诱导的毒性影响,包括大脑。核后上清液(PNS)已被接受为评估外源性物质诱导毒性的体外模型。本研究的目的是验证 PNS 作为研究镉诱导神经毒性的体外模型。在体外,PNS 中以剂量依赖的方式建立了镉诱导的神经毒性。抗氧化酶和非酶抗氧化剂被用作暴露的生物标志物。抗氧化酶活性表现为过氧化氢酶、超氧化物歧化酶和谷胱甘肽 S-转移酶活性显著增加。暴露于镉时,还观察到乙酰胆碱酯酶活性显著增加,钠钾 ATP 酶活性降低。非酶作用也表现为还原型谷胱甘肽和非蛋白巯基活性显著升高,但蛋白巯基的浓度没有显著增加或减少。根据 Cd 对研究中脑结构的毒性,Cd 诱导的氧化应激一直是毒理学研究的焦点,作为神经毒性的可能机制。我们的结果表明,PNS 制剂可用作未来在体外条件下研究外源性物质诱导的神经毒性的模型。