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Effect of sitagliptin, a DPP‐4 inhibitor, against DENA‐induced liver cancer in rats mediated via NF‐κB activation and inflammatory cytokines
Author(s) -
Jiang Weidong,
Wen Dacheng,
Cheng Zhaohua,
Yang Yongsheng,
Zheng Ge,
Yin Fangying
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22220
Subject(s) - sitagliptin , medicine , chemistry , endocrinology , albumin , aspartate transaminase , tumor necrosis factor alpha , transaminase , alkaline phosphatase , biochemistry , enzyme , metformin , diabetes mellitus
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 sitagliptin (10 and 20 mg/kg) prevented the activation of NF‐κB. In conclusion, sitagliptin (10 and 20 mg/kg) has a potential protective effect against DENA‐induced liver cancer by inhibition of inflammation and NF‐κB activation.