Bayrak B B, Koroglu P, Karabulut Bulan O, Yanardag R
Faculty of Engineering, Department of Chemistry, 206543Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey.
Faculty of Medicine, Division of Histology and Embryology, 52965Halic University, Beyoglu, Istanbul, Turkey.
Hum Exp Toxicol. 2021 Feb;40(2):297-309. doi: 10.1177/0960327120947452. Epub 2020 Aug 19.
In this study, both diabetes and Dunning prostate cancer were induced for the first time in Copenhagen rats in vivo. Thus, the effects of metformin against heart tissue damage of these rats were investigated by biochemical methods. Dunning prostate cancer was induced in Copenhagen rats using high metastatic MAT-LyLu cells. The rats were divided as follows: Control group: only injected with 0.9% NaCl for 14 days; Diabetic group: only injected single dose of streptozotocin (STZ) (65 mg/kg); Cancer group: subcutaneously (s.c) inoculated with 2 x 10 MAT-LyLu cells only; Diabetic + cancer (DC) group: inoculated with 2 x 10 MAT-LyLu cells and STZ injection, Cancer + metformin (CM) group: injected with metformin for 14 days after Mat-LyLu cells application; Diabetic + cancer + metformin (DCM) group: metformin administered for 14 days together with STZ and Mat-LyLu cells. At the end of the experimental period, heart tissues were taken. Reduced glutathione and total antioxidant status levels in heart tissues were decreased, whereas lipid peroxidation, advanced oxidized protein products, nitric oxide, homocysteine, and reactive oxygen species levels, total oxidant status and catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and xanthine oxidase activities increased in the diabetic, cancer and DC groups. Treatment with metformin reversed these effects. In conclusion, the present study shows that metformin has a protective effect against heart tissue damage in STZ-induced diabetic rats with Dunning prostate cancer.
在本研究中，首次在哥本哈根大鼠体内诱导出糖尿病和邓宁前列腺癌。因此，采用生化方法研究了二甲双胍对这些大鼠心脏组织损伤的影响。使用高转移性MAT-LyLu细胞在哥本哈根大鼠中诱导出邓宁前列腺癌。大鼠分为以下几组：对照组：仅注射0.9%氯化钠14天；糖尿病组：仅注射单剂量链脲佐菌素（STZ）（65mg/kg）；癌症组：仅皮下接种2×10个MAT-LyLu细胞；糖尿病+癌症（DC）组：接种2×10个MAT-LyLu细胞并注射STZ；癌症+二甲双胍（CM）组：在应用Mat-LyLu细胞后注射二甲双胍14天；糖尿病+癌症+二甲双胍（DCM）组：与STZ和Mat-LyLu细胞一起给予二甲双胍14天。实验期结束时，采集心脏组织。糖尿病组、癌症组和DC组心脏组织中的还原型谷胱甘肽和总抗氧化状态水平降低，而脂质过氧化、晚期氧化蛋白产物、一氧化氮、同型半胱氨酸和活性氧水平、总氧化剂状态以及过氧化氢酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、谷胱甘肽-S-转移酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、乳酸脱氢酶和黄嘌呤氧化酶活性增加。二甲双胍治疗可逆转这些作用。总之，本研究表明二甲双胍对STZ诱导的患有邓宁前列腺癌的糖尿病大鼠的心脏组织损伤具有保护作用。
