Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Halic University, Istanbul, Turkey.
J Biochem Mol Toxicol. 2023 Oct;37(10):e23440. doi: 10.1002/jbt.23440. Epub 2023 Jun 24.
The body can host the spread of prostate cancer cells. Metastases from prostate cancer are more frequently seen in the brain, liver, lungs, and lymph nodes. A well-known antidiabetic drug, metformin, is also known to have antitumor effects. Our study focuses on the evaluation of potential metformin protective effects on brain and cerebellum damage in streptozotocin (STZ)-induced diabetic and Dunning prostate cancer models. In this investigation, six groups of male Copenhagen rats were created: control, diabetic (D), cancer (C), diabetic + cancer (DC), cancer + metformin, and diabetic + cancer + metformin. The brain and cerebellum tissues of the rats were taken after sacrifice. Oxidative stress markers including reduced glutathione level, lipid peroxidation, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, catalase, superoxide dismutase activities, reactive oxygen species, total oxidant and total antioxidant status, lactate dehydrogenase, xanthine oxidase, acetylcholinesterase activities, protein carbonyl contents, nitric oxide and OH-proline levels, sodium potassium ATPase, carbonic anhydrase, and glucose-6-phosphate dehydrogenase activities; glycoprotein levels including hexose, hexosamine, fucose, and sialic acid levels; and histone deacetylase activity as a cancer marker were determined. Oxidative stress markers were impaired and glycoprotein levels and histone deacetylase activity were increased in the D, C, and DC groups. Metformin therapy reversed these effects. Metformin was found to protect the brain and cerebellum of STZ-induced diabetic rats with Dunning prostate cancer from harm caused by MAT-Lylu metastatic cells.
身体可以容纳前列腺癌细胞的扩散。前列腺癌的转移更常见于大脑、肝脏、肺部和淋巴结。一种众所周知的抗糖尿病药物二甲双胍也具有抗肿瘤作用。我们的研究重点是评估二甲双胍对链脲佐菌素（STZ）诱导的糖尿病和 Dunning 前列腺癌模型中大脑和小脑损伤的潜在保护作用。在这项研究中，创建了六组雄性哥本哈根大鼠：对照组、糖尿病组（D）、癌症组（C）、糖尿病+癌症组（DC）、癌症+二甲双胍组和糖尿病+癌症+二甲双胍组。在牺牲后取出大鼠的脑组织和小脑组织。测定氧化应激标志物包括还原型谷胱甘肽水平、脂质过氧化、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶、过氧化氢酶、超氧化物歧化酶活性、活性氧、总氧化剂和总抗氧化状态、乳酸脱氢酶、黄嘌呤氧化酶、乙酰胆碱酯酶活性、蛋白质羰基含量、一氧化氮和 OH-脯氨酸水平、钠钾三磷酸酶、碳酸酐酶和葡萄糖-6-磷酸脱氢酶活性；糖蛋白水平包括己糖、己糖胺、岩藻糖和唾液酸水平；以及作为癌症标志物的组蛋白去乙酰化酶活性。在 D、C 和 DC 组中，氧化应激标志物受损，糖蛋白水平和组蛋白去乙酰化酶活性增加。二甲双胍治疗逆转了这些影响。二甲双胍被发现可以保护 STZ 诱导的糖尿病大鼠的大脑和小脑免受 MAT-Lylu 转移性细胞的伤害。
