Sitagliptin attenuates transient cerebral ischemia/reperfusion injury in diabetic rats: Implication of the oxidative–inflammatory–apoptotic pathway

El-Sahar, Ayman E.; Safar, Marwa M.; Zaki, Hala F.; Attia, Amina S.; Ain-Shoka, Afaf A.

doi:10.1016/j.lfs.2015.01.030

Cited by 63 publications

(72 citation statements)

References 54 publications

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“…This finding is consistent with previous investigations that reported the antiapoptotic effects of sitagliptin. 10,51,52 Finally, sitagliptin is a new anti-diabetic agent that has many advantages over other hypoglycemic agents as weight neutral and a low risk of hypoglycemia as well as lack of drug interactions. Until now no limitation has been reported concerning the use of sitagliptin.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats

El‐Agamy

Abo‐Haded

Elkablawy

2016

Exp Biol Med (Maywood)

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There is a large body of evidence suggesting that inhibitors of dipeptidyl peptidase-4, such as sitagliptin, may exhibit beneficial effects against different inflammatory disorders. This investigation was conducted to elucidate the potential ability of sitagliptin to counteract the injurious effects of doxorubicin in cardiac tissue. Male Wistar rats were pretreated with sitagliptin for 10 days then treated with a single dose of doxorubicin (20 mg/kg, i.p). Electrocardiography, biochemical estimation of serum and tissue markers, and histo-and immunopathological examinations were done. Results have shown that supplementation with sitagliptin resulted in significant improvement of cardiac function with contaminant decrease in serum markers of doxorubicin-induced cardiotoxicity. These results were supported by the histopathological results. Furthermore, a marked protection against oxidative stress was evident through reduction of lipid peroxidation and prevention of reduced glutathione content depletion and superoxide dismutase activity reduction in cardiac tissue of rats pretreated with sitagliptin in combination with doxorubicin. Moreover, sitagliptin ameliorated the activation of nuclear factor kappa-B and the release of inflammatory cytokines, tumour necrosis factoralpha and nitric oxide. Finally, sitagliptin attenuated doxorubicin-induced increase in the expression of pro-apoptotic protein Bax and in the apoptotic marker, caspase-3. Collectively, these data indicate that sitagliptin pretreatment could alleviate doxorubicininduced cardiotoxicity via reducing oxidative damage and its subsequent inflammation and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats

El‐Agamy

Abo‐Haded

Elkablawy

2016

Exp Biol Med (Maywood)

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“…Sitagliptin (SIT) is one of the most well-known incretin enhancers or gliptins, which increases incretin contents due to the inhibition of dipeptidyl peptidase-4 (DPP-4) activity. Previous studies have revealed that SIT may offer cardiovascular and neuropathic protection by antioxidant, anti-inflammatory and anti-apoptotic mechanisms (13)(14)(15)(16)(17)(18)(19). It has also been reported that SIT is able to ameliorate renal ischemia reperfusion injury in rats (20).…”

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confidence: 99%

Sitagliptin ameliorates high glucose-induced cell proliferation and expression of the extracellular matrix in glomerular mesangial cells

Zhang

Wang

Cao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Diabetic nephropathy (DN) is one of the most important causes that leads to end-stage renal disease and the efficacy of strategies currently available for the prevention of DN remains unsatisfactory. Sitagliptin (SIT), which is a dipeptidyl peptidase-4 inhibitor, exhibited a modest beneficial effect on glycated hemoglobin levels and is capable of ameliorating renal ischemia reperfusion injury. By determining the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and fibronectin (FN) levels in high glucose-cultured glomerular mesangial cells (MCs), the present study aimed to assess the anti-proliferative and anti-fibrotic effects of SIT on the therapeutic potential for the prevention of DN and its mechanism. Specifically, cell proliferation was determined via cell counting kit-8 assay, and the expression levels of TGF-β1 and CTGF mRNA were detected by reverse transcription polymerase chain reaction analysis. Furthermore, the secretion of TGF-β1, CTGF, ColIV and FN proteins was measured via enzyme-linked immunosorbent assays. The results demonstrated that high glucose induced the proliferation of MCs and enhanced the expression of TGF-β1, CTGF, ColIV and FN. Furthermore, treatment with SIT inhibited cell proliferation and the expression of TGF-β1, CTGF, ColIV and FN induced by high glucose. In conclusion, SIT inhibits cell proliferation and the expression of the major extracellular matrix proteins induced by high glucose, indicating its value for treating or relieving DN. IntroductionDiabetic nephropathy (DN), which is the leading cause of end-stage kidney failure, is increasing worldwide (1). Mesangial expansion of DN, caused by the proliferation of mesangial cells (MCs) and the excessive accumulation of the extracellular matrix (ECM), is one of the pathological features of DN (2). Hyperglycemia, which activates multiple intracellular signaling factors and results in abnormalities in blood flow and the accumulation of ECM (3-5), has been confirmed as the main initiative factor in the etiology of DN (6), which is one type of kidney fibrosis disease (7-9). In the clinical settings, the major ECM proteins, including collagen type IV (ColIV) and fibronectin (FN), are regarded as the markers of fibrogenesis in numerous kidney fibrosis diseases, such as DN. However, transforming growth factor-β1 (TGF-β1) and its downstream mediator connective tissue growth factor (CTGF) are recognized as fibrogenic cytokines and have a decisive role in the kidney pathophysiology of DN (10,11). At present, MCs are considered as the main type of cells that secrete ECM (12). Therefore, inhibition of MC proliferation and ECM accumulation can be applied as a practical method to treat or delay DN.However, no therapies that are currently available are able to retard the progression of end-stage renal failure and novel treatments in the management of DN are therefore required. Sitagliptin (SIT) is one of the most well-known incretin enhancers or gliptins, which incre...

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“…Enhancement of intracellular Ca2+, NF-kB over expression, and up-regulation of pro-inflammatory cytokines, such as TNF-α, following ischemia induce processes leading to neuronal death (46,47). Several studies confirm that inhibiting the NF-kB signaling pathway could have neuroprotective effects in the model of experimental stroke in rat (48,49). Some studies have also shown that calcium channel blocking could be effective in attenuating of post ischemic damage induced by I/R (50, 51).…”

Section: Discussionmentioning

confidence: 99%

Withania coagulans Protects Striatum from Oxidative Damages Induced by Global Brain Ischemia in Rat

Mahmoudzadeh‐Sagheb

Heidari

Sarbishegi

2017

Jundishapur J Nat Pharm Prod

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Background: Withania coagulans is a traditional plant that possesses diverse pharmacological characteristics including antihyperglycemic, anti-hyperlipidemic, antitumor, anti-inflammatory, and antioxidant effects. Objectives: This study evaluated the effect of preischemic administration of Withania coagulans extract (WCE) on antioxidant status and histopathological alteration of the striatum region in rat model of brain global ischemia reperfusion (I/R). Methods: 48 male Wistar rats were divided into four groups (n = 12): Control, Sham operated (Sham), I/R, and WCE + I/R. The animals received WCE or distilled water by oral gavage for 30 days before I/R except the control group. I/R was induced by two common carotid obstructions for 30 minutes. Three days following I/R, the animals were sacrificed, the brain was removed, and striatum was dissected out. Antioxidant statuses such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and malondialdehyde (MDA) level were measured and histological alteration was investigated in corpus striatum by Nissl and TUNEL staining. Results:The results showed that the CAT, SOD, and GPx activities decreased and MDA level increased in I/R group compare to the control group. Preischemic administration of WCE significantly decreased MDA level and increased antioxidant statuses in the striatum region compared to I/R group (P < 0.001). Histopathological analysis revealed that pretreatment with WCE markedly decreased necrotic and apoptotic neurons (P < 0.001) in striatum and reduced white matter injury induced by I/R. Conclusions: We concluded that WCE by its antioxidant and anti-inflammatory effects could modify ischemia reperfusion damage in rat striatum.

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Sitagliptin attenuates transient cerebral ischemia/reperfusion injury in diabetic rats: Implication of the oxidative–inflammatory–apoptotic pathway

Cited by 63 publications

References 54 publications

Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats

Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats

Sitagliptin ameliorates high glucose-induced cell proliferation and expression of the extracellular matrix in glomerular mesangial cells

Withania coagulans Protects Striatum from Oxidative Damages Induced by Global Brain Ischemia in Rat

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