The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes

Marques, Catarina; Gonçalves, Ana Filipa; Pereira, Patrícia M. R.; Almeida, Daniela Oliveira de; Martins, Beatriz; Fontes‐Ribeiro, Carlos; Reis, Flávio; Fernandes, Rosa

doi:10.1016/j.lfs.2019.116738

Cited by 16 publications

(13 citation statements)

References 65 publications

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“…Prior treatment with Saxagliptin resulted in an increase in activities of the above said enzymes in Isoproterenol-challenged diabetic rats by protecting them from the attack of free radicals, indicating its antioxidant activity. These results align well with another study by Marques et al, 2019 in which Sitagliptin treatment ameliorated renal oxidative stress in rats with diabetes (Marques et al, 2019). Another study highlighted the anti-oxidant potential of gliptins, similar to this study (Bolevich et al, 2019).…”

Section: Discussionsupporting

confidence: 92%

Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats

Kumar

Bhargava

Suchal

et al. 2021

Drug Development Research

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The role of Saxagliptin in diabetes-associated cardiovascular complications is controversial. This study aimed to investigate whether Saxagliptin could prevent Isoproterenolinduced myocardial changes in diabetic rats and to identify the possible mechanism as well. The high-fat diet/low-dose Streptozotocin-induced type 2 diabetic rats were divided into 3 groups: the control group (0.25% CMC for 28 days), the Isoproterenol group (85 mg/kg Isoproterenol for the last 2 days plus 0.25% CMC for 28 days), and the treatment group (10 mg/kg Saxagliptin for 28 days plus 85 mg/kg Isoproterenol for the last 2 days). Hemodynamic measurements were performed, and samples were examined for RAGE and NF-κB expressions, histopathological and ultrastructural changes, AGEs level, myocardial injury markers, oxidative stress, and apoptosis.Saxagliptin significantly recovered cardiac function (p < .001), reverted myocardial injury and oxidative stress levels back to the control value (p < .05 to p < .001). Saxagliptin alleviates Isoproterenol-induced myocardial injury in diabetic rats by suppressing AGE-RAGE pathway.

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Section: Discussionsupporting

confidence: 92%

Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats

Kumar

Bhargava

Suchal

et al. 2021

Drug Development Research

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“…This is due to the diverse adverse effects caused by chronic use of hyperglycemic drugs, and hence, plant sources with negligible adverse effects are now being considered in the development of hyperglycemic drugs. 6 Phytoconstituents with a persuasive antioxidant property have proved to be a breakthrough remedy against DM. Also, they have been highly considered as source of biologically active substance (antioxidants, anti-hyperglycemics and anti-hyperlipidaemics).…”

Section: Introductionmentioning

confidence: 99%

<p>Apigenin-Loaded Solid Lipid Nanoparticle Attenuates Diabetic Nephropathy Induced by Streptozotocin Nicotinamide Through Nrf2/HO-1/NF-kB Signalling Pathway</p>

Li¹,

Bukhari²,

Khan³

et al. 2020

IJN

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Background: Apigenin is known to have a broad-spectrum efficacy in oxidative stress and conditions due to inflammation, although weak absorption, fast metabolic rate and a fast elimination (systemic) limit the pharmacological efficacy of this drug. Hence, we propose the usage of highly bioavailable Apigenin-solid lipid nanoparticles (SLNPs) to recognize such limitations. The defensive function of Apigenin-SLNPs on renal damage induced by streptozotocin (STZ) in animals was studied. Materials and Methods: We initially injected the rats with 35 mg kg −1 streptozocin intraperitoneally, and after 7 days, the rats were then injected 150 mg kg −1 of metformin intragastrically followed by a once-daily intragastric dose of Apigenin-SLNP (25 or 50 mg kg −1) for a continuous period of 30 days. We then measured the level of insulin and blood glucose, superoxide dismutase, catalase and malondialdehyde in the tissues of the kidney. We also observed messenger-RNA expression of Interleukin-1β, Interleukin-6 and Tumor Necrosis Factor-alpha in renal tissue through RT-PCR technique. Moreover, H&E staining and Western blotting observed the histopathological variations and protein expression of nuclear factor erythroid 2-related factor 2/heme oxygenase/Nuclear Factor-κB signaling pathway, respectively. Results: An enhancement in the expressing of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 and a suppression in the expression of Nuclear Factor-κB occurred due to Apigenin-SLNPs treatment, which was a result of the protective mechanism of Apigenin-SLNPs which is because of not only its anti-inflammatory function (by inhibition of release of inflammatory factors) but also their anti-oxidant activity (through reduction of lipid peroxidation production). Conclusion: We found that a protective effect on diabetic nephropathy was shown due to Apigenin-SLNPs, in rats induced with streptozocin maybe through the pathway of nuclear factor erythroid 2-related factor 2/heme oxygenase-1/Nuclear Factor-κB.

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“…Dipeptidyl peptidase-4 inhibitors (DPP4i) are effective for the treatment of residual proteinuria in DN, a fact that is evidenced in a recent meta-analysis of the effects of sitagliptin in T2DM patients [318]. Sitagliptin also display in vitro and in vivo nephroprotective actions, including antioxidant [319,320], lipotoxicity-mediated inflammation [321] and antifibrotic actions [322].…”

Section: Novel Antidiabetic Drugs With Anti-inflammatory Actions In Dnmentioning

confidence: 99%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

187

127

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Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

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The dipeptidyl peptidase 4 inhibitor sitagliptin improves oxidative stress and ameliorates glomerular lesions in a rat model of type 1 diabetes

Cited by 16 publications

References 65 publications

Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats

Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats

<p>Apigenin-Loaded Solid Lipid Nanoparticle Attenuates Diabetic Nephropathy Induced by Streptozotocin Nicotinamide Through Nrf2/HO-1/NF-kB Signalling Pathway</p>

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

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