Abstract：
Doxorubicin is a highly effective anticancer agent that causes hepatotoxicity and cardiotoxicity in patients. Fibroblast growth factor 21, a well-known regulator of glucose and lipid metabolism, exerts cardioprotective effects. Gemigliptin and dipeptidyl peptidase-4 inhibitors are widely used in the treatment of patients with type 2 diabetes. The protective effects of gemigliptin on hepatotoxicity via the increase in fibroblast growth factor 21 expression has not yet been elucidated. This study was designed to investigate the protective effects of gemigliptin against doxorubicin-induced hepatotoxicity via the upregulation of fibroblast growth factor 21 expression in the cultured murine hepatocyte cell line, AML12.
Murine hepatocyte AML12 cells were treated with doxorubicin, fibroblast growth factor 21 and gemigliptin in 0.5% fetal bovine serum medium for 24 h at the indicated doses. Cells were transfected with the fibroblast growth factor 21 small interfering RNA for 24 h, followed by protein isolation.
Fibroblast growth factor 21 expression levels were increased during doxorubicin-induced hepatotoxicity in the murine hepatocyte AML12 cells. Fibroblast growth factor 21 treatment prevented doxorubicin-induced hepatotoxicity by attenuating apoptosis. Gemigliptin prevented doxorubicin-induced hepatotoxicity by upregulating fibroblast growth factor 21 expression. However, the protective effects of gemigliptin were blocked by fibroblast growth factor 21 inhibition in doxorubicin-treated AML12 cells.
These results indicate that gemigliptin exhibits protective effects against doxorubicin-induced hepatotoxicity by upregulating the fibroblast growth factor 21 expression levels in the cultured murine hepatocyte AML12 cells.
Murine hepatocyte AML12 cells were treated with doxorubicin, fibroblast growth factor 21 and gemigliptin in 0.5% fetal bovine serum medium for 24 h at the indicated doses. Cells were transfected with the fibroblast growth factor 21 small interfering RNA for 24 h, followed by protein isolation.
Fibroblast growth factor 21 expression levels were increased during doxorubicin-induced hepatotoxicity in the murine hepatocyte AML12 cells. Fibroblast growth factor 21 treatment prevented doxorubicin-induced hepatotoxicity by attenuating apoptosis. Gemigliptin prevented doxorubicin-induced hepatotoxicity by upregulating fibroblast growth factor 21 expression. However, the protective effects of gemigliptin were blocked by fibroblast growth factor 21 inhibition in doxorubicin-treated AML12 cells.
These results indicate that gemigliptin exhibits protective effects against doxorubicin-induced hepatotoxicity by upregulating the fibroblast growth factor 21 expression levels in the cultured murine hepatocyte AML12 cells.
摘要：
阿霉素是一种非常有效的抗癌剂，可引起患者的肝毒性和心脏毒性。成纤维细胞生长因子21，一种众所周知的葡萄糖和脂质代谢调节剂，发挥心脏保护作用。吉格列汀和二肽基肽酶-4抑制剂广泛用于治疗2型糖尿病患者。吉格列汀通过增加成纤维细胞生长因子21表达对肝毒性的保护作用尚未阐明。本研究旨在研究吉格列汀通过上调成纤维细胞生长因子21的表达对阿霉素诱导的肝毒性的保护作用。AML12.
用阿霉素处理小鼠肝细胞AML12细胞，成纤维细胞生长因子21和吉格列汀在0.5%胎牛血清培养基中以指定剂量培养24小时。用成纤维细胞生长因子21小干扰RNA转染细胞24小时，然后是蛋白质分离。
在多柔比星诱导的小鼠肝细胞AML12细胞中，成纤维细胞生长因子21的表达水平增加。成纤维细胞生长因子21治疗通过减弱细胞凋亡来预防阿霉素诱导的肝毒性。吉格列汀通过上调成纤维细胞生长因子21的表达来预防阿霉素诱导的肝毒性。然而,在多柔比星处理的AML12细胞中,成纤维细胞生长因子21抑制阻断了吉格列汀的保护作用.
这些结果表明，吉格列汀通过上调培养的鼠肝细胞AML12细胞中的成纤维细胞生长因子21表达水平而表现出对阿霉素诱导的肝毒性的保护作用。
用阿霉素处理小鼠肝细胞AML12细胞，成纤维细胞生长因子21和吉格列汀在0.5%胎牛血清培养基中以指定剂量培养24小时。用成纤维细胞生长因子21小干扰RNA转染细胞24小时，然后是蛋白质分离。
在多柔比星诱导的小鼠肝细胞AML12细胞中，成纤维细胞生长因子21的表达水平增加。成纤维细胞生长因子21治疗通过减弱细胞凋亡来预防阿霉素诱导的肝毒性。吉格列汀通过上调成纤维细胞生长因子21的表达来预防阿霉素诱导的肝毒性。然而,在多柔比星处理的AML12细胞中,成纤维细胞生长因子21抑制阻断了吉格列汀的保护作用.
这些结果表明，吉格列汀通过上调培养的鼠肝细胞AML12细胞中的成纤维细胞生长因子21表达水平而表现出对阿霉素诱导的肝毒性的保护作用。
