Abolaji Amos Olalekan, Fasae Kehinde Damilare, Iwezor Chizim Elizabeth, Farombi Ebenezer Olatunde
Department of Biochemistry, Drosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Toxicol Res (Camb). 2020 Jun 3;9(4):346-352. doi: 10.1093/toxres/tfaa032. eCollection 2020 Jul.
D-penicillamine (DPA) is an amino-thiol that has been established as a copper chelating agent for the treatment of Wilson's disease. DPA reacts with metals to form complexes and/or chelates. Here, we investigated the survival rate extension capacity and modulatory role of DPA on Cu-induced toxicity in Adult Wild type (Harwich strain) flies were exposed to Cu (1 mM) and/or DPA (50 μM) in the diet for 7 days. Additionally, flies were exposed to acute Cu (10 mM) for 24 h, followed by DPA (50 μM) treatment for 4 days. Thereafter, the antioxidant status [total thiol (T-SH) and glutathione (GSH) levels and glutathione S-transferase and catalase activities] as well as hydrogen peroxide (HO) level and acetylcholinesterase activity were evaluated. The results showed that DPA treatment prolongs the survival rate of by protecting against Cu-induced lethality. Further, DPA restored Cu-induced depletion of T-SH level compared to the control ( < 0.05). DPA also protected against Cu (1 mM)-induced inhibition of catalase activity. In addition, DPA ameliorated Cu-induced elevation of acetylcholinesterase activity in the flies. The study may therefore have health implications in neurodegenerative diseases involving oxidative stress such as Alzheimer's disease.
D-青霉胺（DPA）是一种氨基硫醇，已被确立为用于治疗威尔逊氏病的铜螯合剂。DPA与金属反应形成络合物和/或螯合物。在此，我们研究了DPA对铜诱导的成年野生型（哈维奇品系）果蝇毒性的存活率延长能力和调节作用。果蝇在饮食中暴露于铜（1 mM）和/或DPA（50 μM）7天。此外，果蝇暴露于急性铜（10 mM）24小时，随后用DPA（50 μM）处理4天。此后，评估抗氧化状态[总硫醇（T-SH）和谷胱甘肽（GSH）水平以及谷胱甘肽S-转移酶和过氧化氢酶活性]以及过氧化氢（HO）水平和乙酰胆碱酯酶活性。结果表明，DPA处理通过防止铜诱导的致死性来延长果蝇的存活率。此外，与对照组相比，DPA恢复了铜诱导的T-SH水平的消耗（P < 0.05）。DPA还防止了铜（1 mM）诱导的过氧化氢酶活性抑制。此外，DPA改善了果蝇中铜诱导的乙酰胆碱酯酶活性升高。因此，该研究可能对涉及氧化应激的神经退行性疾病如阿尔茨海默病具有健康意义。
