Department of Chemistry, Faculty of Science, Atatürk University, Erzurum, Turkey.
Department of Molecular Biology and Genetics, Faculty of Science, Atatürk University, Erzurum, Turkey.
J Biochem Mol Toxicol. 2020 Jul;34(7):e22496. doi: 10.1002/jbt.22496. Epub 2020 Mar 20.
Despite the fact that the use of antibiotics is increasing worldwide, it is clear that antibiotics can lead to oxidative stress. This is the first study to make a comparison of the impact of frequently prescribed antibiotics, including amoxicillin, gentamicin, and cefazolin sodium, on the gene, protein, and activity of glutathione reductase (GR), which is one of the primary antioxidant enzymes, in mouse liver and kidney tissues. First, the GR enzyme was purified by the 2',5'-ADP Sepharose 4B affinity chromatography with a specific activity of 84.615 EU/mg protein and 9.63 EU/mg protein from the mouse liver and kidney, respectively. The in vitro inhibitory effects of the antibiotics in question was determined. While cefazolin sodium did not exhibit any inhibitory effect, gentamicin and amoxicillin inhibited GR activity in both tissues. Furthermore, the in vivo effects of these drugs were investigated, and amoxicillin and cefazolin sodium-inhibited GR activity in both liver and kidney tissues, while gentamicin did not have any effect on the kidney. Besides, while gentamicin downregulated and cefazolin sodium upregulated Gr gene expression, amoxicillin did not alter it. Protein expression was only affected by the administration of cefazolin sodium in the kidney. This study is important as it demonstrates that while amoxicillin and gentamicin showed parallel effects on the GR activity in liver and kidney tissues both in vitro and in vivo, cefazolin sodium had a very strong effect on hepatic and renal GR in vivo. Furthermore, the antibiotics used in this study induced oxidative stress in both tissues.
尽管抗生素的使用在全球范围内不断增加,但很明显,抗生素会导致氧化应激。这是第一项比较包括阿莫西林、庆大霉素和头孢唑林钠在内的常用抗生素对小鼠肝、肾组织中谷胱甘肽还原酶(GR)的基因、蛋白和活性的影响的研究。首先,通过 2',5'-ADP Sepharose 4B 亲和层析法从鼠肝、肾组织中分别纯化 GR 酶,比活分别为 84.615 EU/mg 蛋白和 9.63 EU/mg 蛋白。测定了抗生素的体外抑制作用。头孢唑林钠没有表现出任何抑制作用,而庆大霉素和阿莫西林抑制了两种组织中的 GR 活性。此外,还研究了这些药物的体内作用,阿莫西林和头孢唑林钠抑制了肝、肾组织中的 GR 活性,而庆大霉素对肾脏没有影响。此外,庆大霉素下调和头孢唑林钠上调 Gr 基因表达,而阿莫西林没有改变它。蛋白表达仅受头孢唑林钠在肾脏中的影响。这项研究很重要,因为它表明阿莫西林和庆大霉素在体外和体内均对肝、肾组织中的 GR 活性表现出平行作用,而头孢唑林钠对肝、肾 GR 具有很强的体内作用。此外,本研究中使用的抗生素在两种组织中均诱导了氧化应激。