Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice

Hewedy, Wafaa A.

doi:10.1590/s2175-97902019000418482

Cited by 3 publications

(1 citation statement)

References 41 publications

(44 reference statements)

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“…Moreover, Pintana et al [ 44 ] demonstrated that STG attenuated brain oxidative stress and restored hippocampal mitochondrial function in rats. Indirect mechanisms for antioxidant activity of STG upregulated the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) [ 45 ]. Nrf2 is a key transcription factor involved in stress response to oxidative impairment and controlling the expression of antioxidants [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Khodir

Faried

Abd-Elhafiz

et al. 2022

BioMed Research International

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Vascular dementia (VaD) is the second most prevalent type of dementia characterized by progressive cognitive deficits and is a major risk factor for the development of Alzheimer’s disease and other neurodegenerative disorders. This study is aimed at determining the potential neuroprotective effect of sitagliptin (STG) on cognitive deficits in L-methionine-induced VaD in rats and the possible underlying mechanisms. 30 adult male Wistar albino rats were divided equally ( n = 10 ) into three groups: control, VaD, and VaD + STG groups. The cognitive performance of the animals was conducted by open field, elevated plus maze, Y-maze, novel object recognition, and Morris water maze tests. Serum homocysteine, TNF-α, IL-6, IL-10, total cholesterol, and triglycerides levels were assessed together with hippocampal MDA, SOD, and BDNF. Histopathological and immunohistochemical assessments of the thoracic aorta and hippocampus (CA1 region) were also performed. Chronic L-methionine administration impaired memory and learning and induced anxiety. On the other hand, STG protected against cognitive deficits through improving oxidative stress biomarkers, inflammatory mediators, lipid profiles, and hippocampus level of BDNF as well as decreasing caspase-3 and GFAP and increasing Ki-67 immunoreactions in the hippocampus. Also, STG improved the endothelial dysfunction via upregulation of aortic eNOS immunoreaction. STG improved the cognitive deficits of L-methionine-induced VaD by its antioxidant, anti-inflammatory, antiapoptotic, and neurotrophic effects. These findings suggest that STG may be a promising future agent for protection against VaD.

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Section: Discussionmentioning

confidence: 99%

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Khodir

Faried

Abd-Elhafiz

et al. 2022

BioMed Research International

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

et al. 2021

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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.

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The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant Enterolobium contortisiliquum; A Case of Two Soul Mates Meeting

et al. 2023

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Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from Crotalus durissus terrificus total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity. A Kunitz-like EcTI inhibitor protein with a molecular mass of 20 kDa was isolated from Enterolobium contortisiliquum and showed high trypsin inhibition. Thus, the objective of this work is to verify the possible inhibition of the pharmacological activities of Cdtsp-2 by the Kutinz-type inhibitor EcTI. To isolate Cdtsp-2 from total C. d. terrificus venom, we used three-step chromatographic HPLC. Using the mice paw edema model, we observed an edematogenic effect, myotoxicity and hepatotoxicity caused by Cdtsp-2. In vitro and in vivo experiments showed that the alterations in hemostasis caused by Cdtsp-2 are crucial for the development of marked hepatotoxicity and that EcTI significantly inhibits the enzymatic and pharmacological activities of Cdtsp-2. Kunitz-like inhibitor may be a viable alternative for the development of ancillary treatments against the biological activities of venoms.

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Effects of treatment with sitagliptin on hepatotoxicity induced by acetaminophen in mice

Cited by 3 publications

References 41 publications

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

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

The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant Enterolobium contortisiliquum; A Case of Two Soul Mates Meeting

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