Chemistry Department, Faculty of Science, Damietta University, Damietta, 34517, Egypt.
Amino Acids. 2023 May;55(5):679-693. doi: 10.1007/s00726-023-03261-w. Epub 2023 Mar 26.
Doxorubicin (DOXO) is a well-known cancer chemotherapeutic. However, its toxic effect on the heart limits its clinical application. This study aimed to assess the effectiveness of glycine administration to counteract the DOXO-induction of cardiomyopathy in mice. Fifty male albino mice were divided into five groups (n = 10/group) as follows: control, DOXO, Gp100, Gp150, and Gp200. Histopathological examination of the heart, and biochemical examinations for heart function (creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)), inflammation (tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10)), oxidative stress (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, nitric oxide (NO), and uric acid), kidney function (urea and creatinine), and minerals (calcium, phosphorus, sodium, and potassium) were carried out. Cardiomyopathy induced by DOXO treatment (15 mg/kg total dose) was ascertained via pathological alterations seen in heart tissue and verified biochemically via increases (P < 0.001) in CPK, LDH, AST, TNF-α, IL-10, MDA, NO, Na, and K levels along with decreases (P < 0.001) in GSH, SOD, catalase, and uric acid. Glycine co-treatment, using doses of 100, 150, and 200 mg/kg, in a dose-dependent manner, displayed ameliorated heart architecture, significantly (P < 0.001) improved biochemical heart function tests, reduced oxidative stress and inflammation, and controlled mineral levels. The positive actions of glycine in DOXO-induced cardiotoxicity amelioration via modulating oxidative stress, inflammation, and immunity are confirmed. Glycine antioxidative properties may be behind its positive outcomes. Finally, we present glycine as a worthy possible option against DOXO-induced heart damage after more validation.
多柔比星（DOXO）是一种著名的癌症化疗药物。然而，其对心脏的毒性作用限制了其临床应用。本研究旨在评估甘氨酸给药对减轻 DOXO 诱导的小鼠心肌病的疗效。50 只雄性白化小鼠被分为五组（每组 10 只）：对照组、DOXO 组、Gp100 组、Gp150 组和 Gp200 组。对心脏进行组织病理学检查，对心脏功能（肌酸磷酸激酶（CPK）、乳酸脱氢酶（LDH）和天冬氨酸氨基转移酶（AST））、炎症（肿瘤坏死因子-α（TNF-α）和白细胞介素 10（IL-10））、氧化应激（丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、过氧化氢酶、一氧化氮（NO）和尿酸）、肾功能（尿素和肌酐）和矿物质（钙、磷、钠和钾）进行生化检测。通过心脏组织的病理改变确定 DOXO 治疗（15mg/kg 总剂量）诱导的心肌病，并通过 CPK、LDH、AST、TNF-α、IL-10、MDA、NO、Na 和 K 水平的升高（P<0.001）以及 GSH、SOD、过氧化氢酶和尿酸水平的降低（P<0.001）得到生化验证。甘氨酸以 100、150 和 200mg/kg 的剂量进行联合治疗，呈剂量依赖性，改善了心脏结构，显著（P<0.001）改善了生化心脏功能测试，降低了氧化应激和炎症，控制了矿物质水平。甘氨酸通过调节氧化应激、炎症和免疫改善 DOXO 诱导的心脏毒性的积极作用得到了证实。甘氨酸的抗氧化特性可能是其积极结果的原因。最后，我们提出甘氨酸作为一种有价值的选择，可能对抗 DOXO 诱导的心脏损伤，需要进一步验证。
