Effect of sitagliptin, a DPP‐4 inhibitor, against DENA‐induced liver cancer in rats mediated via NF‐κB activation and inflammatory cytokines

作者：Weidong Jiang, Dacheng Wen, Zhaohua Cheng, Yongsheng Yang, Zheng Ge, Fangying Yin · 发表于：Journal of Biochemical and Molecular Toxicology · 年份：2018 · DOI：10.1002/jbt.22220 · 被引用次数：33 · 研究领域：Cancer, Lipids, and Metabolism、Peroxisome Proliferator-Activated Receptors、Drug Transport and Resistance Mechanisms

The target of the current research was to investigate the anticancer activity of sitagliptin on diethylnitrosamine (DENA)-induced cancer in the liver. Wistar rats were treated with or without sitagliptin before DENA treatment. We detected liver weight, blood glucose, and histopathology of the liver. Serum biochemical markers like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), serum alkaline phosphatase (SALP), gamma-glutamyl transpeptidase (GGTP), total bilirubin (TBR), total protein (TPR), and albumin (ALB) were also evaluated. In addition, lipid profile parameters comprising total cholesterol (TC), triglycerides, and high-density lipoprotein were also measured. Inflammatory mediators like interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were determined in liver homogenate. Furthermore, the activity of nuclear factor (NF-κB) was also measured. Our results showed that sitagliptin (10 and 20 mg/kg) in a dose-dependent manner expressively decreased the DENA-induced elevation of SGPT, SGOT, SALP, and GGTP. Whereas sitagliptin (10 and 20 mg/kg) in a dose-dependent mode reduced the level of TBR and increased the TPR and ALB as well as improved the liver histopathology alterations in DENA-exposed rats. Lipid profile was also restored by the sitagliptin (10 and 20 mg/kg) in a DENA-treated rats. The level of IL-1β, IL-6, and TNF-α were suggestively suppressed. Moreover, pretreatment with sitaglip...