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

Abstract

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.

Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM‐1 and VEGF‐A

“…Sitagliptin pretreatment improved the aforementioned parameters indicating its antioxidant and anti‐inflammatory activity matching with the previous studies of Omolekulo, Michael, and Olatunji (), Khedr, Ahmed, Kamel, and Raafat (), Jiang et al (), Abdelrahman et al, () and Chang et al, ().…”

Antitumor activity of sitagliptin and vitamin B12 on Ehrlich ascites carcinoma solid tumor in mice

“…[ 29 ] The solid tumors were visually apparent (50–100 mm 3 ) after 5 days of inoculation. To examine its possible protective effect against tumor development, vitamin B12 was administered (1.5 mg/kg/d) to a group of mice for 4 weeks before EAC cell injection; this group of mice was called “the B12‐protected group.” After tumor development, the mice were distributed equally into eight groups, with eight mice each, as follows: the control group that was kept for 3 weeks and did not receive any treatment; the B12‐treated group that was treated with oral B12 (1.5 mg/kg/d) [ 30 ] for 21 days; the DOX group that was injected I/P with DOX (2 mg/kg/d) for 21 days [ 31 ] ; the B12 + DOX group that received oral B12 (1.5 mg/kg/d) and was injected I/P with DOX (2 mg/kg/d) for 21 days; the sitagliptin 10 (S10) group that received oral sitagliptin (10 mg/kg/d) [ 32,33 ] for 21 days; the sitagliptin 20 (S20) group that received oral sitagliptin (20 mg/kg/d) [ 32,33 ] for 21 days; the S10 + DOX group that received a combination of oral sitagliptin (10 mg/kg/d) and I/P DOX injection (2 mg/kg/d) for 21 days; and the S20 + DOX group that received a combination of oral sitagliptin (20 mg/kg/d) and I/P DOX injection (2 mg/kg/d) for 21 days.…”

A new perspective on the pleiotropic blood pressure improvement effect of sitagliptin: downregulation of miRNA-155 and miRNA-21

“…Infl ammatory parameters in different kinds of pathologies and the effect of sitagliptin on these processes are tested generally. In a liver cancer study, sitagliptin decreased IL-6, IL-1β and TNF-α levels (41). In a clinical study comparing sitagliptin with another oral antidiabetic in type-2 DM, sitagliptin has been reported to signifi cantly reduced CRP levels much more effectively (42).…”