Antioxidant Effects of Sitagliptin in a Rat Model of Intestinal Ischemia/Reperfusion Injury

Khedr, Rehab M.; Ahmed, Ashraf M.; Kamel, Rehab; Rafaat, Eman

doi:10.21608/aprh.2020.49560.1119

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dipeptidyl peptidase-4 inhibitors are among the drugs studied for their potential use for new therapeutic purposes, a strategy referred to as drug repurposing or repositioning [ 9 ]. Recently, a large body of evidence has accumulated showing sitagliptin effectiveness in lessening tissue damage during intestinal [ 24 , 32 ], cardiac [ 23 , 33 ], cerebral [ 30 ], testicular [ 31 ] and renal [ 28 , 29 ] ischemia-reperfusion insult. Likewise, sitagliptin has reduced the histopathological signs of injury and decreased the serum activities of ALT and AST in animal models of hepatic IR [ 21 , 22 , 25 , 26 ], acting via mechanisms employing its anti-inflammatory and antioxidative properties.…”

Section: Discussionmentioning

confidence: 99%

“…Several experimental studies have demonstrated pleiotropic properties, including the antioxidative, anti-inflammatory and antiapoptotic action of sitagliptin [ 18 , 19 ], a well-tolerated DPP-4 inhibitor with moderate side effects [ 20 ]. Accordingly, we [ 21 , 22 ], as well as others [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], have shown that sitagliptin alleviates injury caused by IR procedure. However, the molecular background has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

et al. 2021

View full text Add to dashboard Cite

A possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The expression and/or concentration of inflammation and oxidative stress-involved factors have been determined in rat liver homogenates using quantitative RT-PCR and Luminex® xMAP® technology and markers of nitrative and halogenative stress were quantified using targeted metabolomics (LC-MS/MS). Animals (n = 36) divided into four groups were treated with sitagliptin (5 mg/kg) (S and SIR) or saline solution (C and IR), and the livers from IR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). The midkine expression (by 2.2-fold) and the free 3-nitrotyrosine (by 2.5-fold) and IL-10 (by 2-fold) concentration were significantly higher and the Nox4 expression was lower (by 9.4-fold) in the IR than the C animals. As compared to IR, the SIR animals had a lower expression of interleukin-6 (by 4.2-fold) and midkine (by 2-fold), a lower concentration of 3-nitrotyrosine (by 2.5-fold) and a higher Nox4 (by 2.9-fold) and 3-bromotyrosine (by 1.4-fold). In conclusion, IR disturbs the oxidative, nitrative and halogenative balance and aggravates the inflammatory response in the liver, which can be attenuated by low doses of sitagliptin.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Among these, gliptins (dipeptidyl peptidase-4 (DPP-4) inhibitors and primarily antidiabetics) arouse a growing interest. Gliptins, including their protagonist, sitagliptin, have been shown to exert cytoprotective effects in animal models of hepatic [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ], cardiac [ 19 , 20 ], renal [ 21 , 22 , 23 ], cerebral [ 24 ], testicular [ 25 ], and intestinal [ 26 , 27 ] IR injury. Although anti-inflammatory, antioxidant, and antiapoptotic properties of gliptins seem to be implicated, the underlying molecular mechanisms are to be explained.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury

Krzystek−Korpacka

Fleszar

Fortuna

et al. 2021

IJMS

View full text Add to dashboard Cite

Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI2, PGE2, and 13,14-dihydro-PGE1 were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD2 and 15-deoxy-12,14-PGJ2. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD2 and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling.

show abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury

Mohammed,

Mohamed,

Zeid

et al. 2024

Beni-Suef Univ J Basic Appl Sci

View full text Add to dashboard Cite

Background Ischemia-reperfusion injury (I/R) for skeletal muscle usually results from vascular injuries or trauma. Sitagliptin (STG) is an effective member of the dipeptidyl peptidase-4 (DPP-4) inhibitors drug family that plays roles in oxidative stress regulation, inflammation, and autophagy control. In this study, we evaluated the protective roles of STG against I/R of gastrocnemius muscle and the underlying mechanisms. Materials and methods Forty-eight mice were randomly allocated into three groups: Group I (n = 24): control group which was subdivided equally into subgroup IA; negative control, subgroup IB; sitagliptin (STG), Group II (n = 12): ischemia–reperfusion injury (I/R), and Group III (n = 12): sitagliptin pretreatment (300 mg/kg/ day; p.o.) for two weeks followed by ischemia–reperfusion injury (STG + I/R). We measured SOD activity and MDA level to assess oxidative stress. Moreover, GLP-1/p-PI3K/ p-AKT expression levels were investigated. Autophagy was estimated by assessing lncRNA H19, Beclin-1 and ATG7 expression by RT-qPCR analysis. Inflammatory markers were assessed by iNOS and NF‐κB expression using immunohistochemistry. Results Our results revealed that STG pretreatment significantly attenuated oxidative stress and inflammation and upregulated GLP-1, p-PI3K, and p-AKT protein levels. Also, LnRNA H19, Becline-1, and ATG7 mRNA expression were downregulated as well as decrease the expression of the inflammatory markers iNOS and NF‐κB with STG pretreatment. Conclusion Our results highlighted the useful effects of Sitagliptin during hind limb I/R that could be mediated by antioxidant, anti-inflammatory effects, and attenuation of excessive autophagy.

show abstract

Antioxidant Effects of Sitagliptin in a Rat Model of Intestinal Ischemia/Reperfusion Injury

Cited by 3 publications

References 0 publications

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion

Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury

Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin ameliorates inflammation and autophagy in mice hindlimb ischemia–reperfusion injury

Contact Info

Product

Resources

About