Nicorandil enhances the efficacy of mesenchymal stem cell therapy in isoproterenol-induced heart failure in rats

Mohamed, Sarah S.; Ahmed, Lamiaa A.; Attia, Walid A.; Khattab, Mahmoud M.

doi:10.1016/j.bcp.2015.10.004

Cited by 37 publications

(42 citation statements)

References 59 publications

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“…However, in animal models, the chronic treatment with ISO causes severe stress to the cardiomyocytes resulting in hypertrophy and myocardial infarct, which are similar to those observed in human [15, 16] and are closely related to oxidative stress and inflammation [17, 18]. In contrast, there are no evidences of the effects of ISO treatment on renal pathophysiology.…”

Section: Introductionmentioning

confidence: 72%

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

Ponte¹,

Casare²,

Costa-Pessoa³

et al. 2017

Kidney Blood Press Res

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Background/Aims: To assess the possible contribution of the β-adrenergic overstimulation in early stages of renal injury, the present study evaluated, in rats, the effects of the β-adrenoceptor agonist isoproterenol (ISO) on renal function and morphology, as well as the renal mRNA and protein expression of the NADPH oxidase isoform 4 (Nox 4) and subunit p22^phox, endoplasmic reticulum (ER) stress, pro-inflammatory, pro-apoptotic and renin-angiotensin system (RAS) components. Methods: Wistar rats received ISO (0.3 mg.kg^-1.day^-1 s.c.) or vehicle (control) for eight days. At the end of the treatment, food and water intake, urine output and body weight gain were evaluated and renal function studies were performed. Renal tissue was used for the morphological, quantitative PCR and immunohistochemical studies. Results: ISO did not change metabolic parameters or urine output. However it induced a decrease in renal blood flow and an increase in the filtration fraction. These changes were accompanied by increased cortical mRNA and protein expression for the renal oxidative stress components including Nox 4 and p22^phox; ER stress, pro-inflamatory, pro-apoptotic as well as RAS components. ISO also induced a significant increase in medullar renin protein expression. Conclusion: These findings support relevant information regarding the contribution of specific β-adrenergic hyperactivity in early stage of renal injury, indicating the reactive oxygen species, ER stress and intrarenal RAS as important factors in this process.

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Section: Introductionmentioning

confidence: 72%

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

Ponte¹,

Casare²,

Costa-Pessoa³

et al. 2017

Kidney Blood Press Res

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“…Sympathetic nervous system (SNS) activity is essential for cardiovascular homeostasis, but SNS hyperactivity is associated with the development and progression of cardiovascular disorders including cardiac oxidative stress and inflammation, leading to cardiac remodeling, infarction and failure [22][23][24][25] . SNS hyperactivity-associated β1 adrenergic receptor (β1-AR) overstimulation in heart promotes cardiac hypertrophy 25,26 .…”

mentioning

confidence: 99%

“…SNS hyperactivity-associated β1 adrenergic receptor (β1-AR) overstimulation in heart promotes cardiac hypertrophy 25,26 . On the other hand, persistent stimulation of β2-AR causes NADPH oxidase-induced ROS generation and inflammation leading to necrosis, fibrosis and MI 22,24,27 . Importantly, there is a high prevalence of SNS hyperactivity in diabetic patients, which makes them more vulnerable to cardiovascular diseases.…”

mentioning

confidence: 99%

“…Recent studies showing in-vivo antioxidant, anti-inflammatory and cardioprotective actions of canagliflozin raise the possibility that canagliflozin may be clinically useful in cardiac oxidative damage including that caused by SNS hyperactivity. Therefore, in the present study we first induced a model of chronic SNS overstimulation by administering the non-selective β-AR agonist isoprenaline (ISO) that produced profound cardiac injuries via ROS/RNS generation, inflammation and apoptosis 22,24,25 , and then investigated protective effects of canagliflozin and their underlying molecular mechanisms. We found that canagliflozin augmented heart function marker in ISO-treated rats by stimulating multiple antioxidant and anti-inflammatory signaling pathways involving AMPK, Akt, eNOS, Nrf2 and HO-1 to counter ISO-induced oxidative damage caused by increased iNOS, TGF-β, Nox4, Bax and active caspase-3.…”

mentioning

confidence: 99%

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Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways

Hasan

Lasker

Hasan

et al. 2020

Sci Rep

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The antidiabetic drug canagliflozin is reported to possess several cardioprotective effects. However, no studies have investigated protective effects of canagliflozin in isoprenaline (ISO)-induced cardiac oxidative damage-a model mimicking sympathetic nervous system (SNS) overstimulation-evoked cardiac injuries in humans. Therefore, we investigated protective effects of canagliflozin in ISOinduced cardiac oxidative stress, and their underlying molecular mechanisms in Long-Evans rat heart and in HL-1 cardiomyocyte cell line. Our data showed that ISO administration inflicts pro-oxidative changes in heart by stimulating production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In contrast, canagliflozin treatment in ISO rats not only preserves endogenous antioxidants but also reduces cardiac oxidative stress markers, fibrosis and apoptosis. Our Western blotting and messenger RNA expression data demonstrated that canagliflozin augments antioxidant and anti-inflammatory signaling involving AMP-activated protein kinase (AMPK), Akt, endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In addition, canagliflozin treatment attenuates pro-oxidative, pro-inflammatory and proapoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-β), NADPH oxidase isoform 4 (Nox4), caspase-3 and Bax. Consistently, canagliflozin treatment improves heart function marker in ISO-treated rats. In summary, we demonstrated that canagliflozin produces cardioprotective actions by promoting multiple antioxidant and antiinflammatory signaling. Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, belongs to a new class of antidiabetic drugs prescribed for the management of type 2 diabetes mellitus (T2DM) 1. Accumulating evidence suggests that canagliflozin exhibits a range of cardiovascular effects that are independent of glucose lowering. According to recent preclinical and clinical data, canagliflozin treatment significantly reduced risk of cardiovascular death, myocardial infarction (MI), stroke and hospitalization due to heart failure in both diabetic and non-diabetic subjects 2-5. Proposed mechanisms for cardiovascular benefits of canagliflozin include improvement of cardiac metabolism and diastolic function, reduction of vascular stiffness, and an overall reduction of blood pressure 5-9. A growing body of evidence suggests that canagliflozin possess antioxidant and anti-inflammatory actions in various cellbased and animal models 10-14. Canagliflozin was shown to reduce vascular inflammation and atherosclerosis by

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“…Entretanto, sua interação com os receptores β1 no tecido cardíaco pode induzir hipertrofia cardíaca e infarto no miocárdio (DAVEL et al, 2008;MOHAMED et al, 2015). Assim, animais tratados com isoproterenol, a médio ou longo prazo, são bem estabelecidos como modelos de hipertrofia cardíaca ou infarto do miocárdio, respectivamente (DAVEL et al, 2008;MOHAMED et al, 2015).…”

Section: Isoproterenol -Agonista Sintético Dos Receptores β-Adrenérgicosunclassified

Estudo da estimulação crônica dos receptores β-adrenérgicos na função e morfologia renal e na ativação do sistema renina-angiotensina intrarrenal.

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Nicorandil enhances the efficacy of mesenchymal stem cell therapy in isoproterenol-induced heart failure in rats

Cited by 37 publications

References 59 publications

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways

Estudo da estimulação crônica dos receptores β-adrenérgicos na função e morfologia renal e na ativação do sistema renina-angiotensina intrarrenal.

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Nicorandil enhances the efficacy of mesenchymal stem cell therapy in isoproterenol-induced heart failure in rats

Cited by 37 publications

References 59 publications

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

The Role of β-Adrenergic Overstimulation in the Early Stages of Renal Injury

Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways

Estudo da estimulação crônica dos receptores &#946;-adrenérgicos na função e morfologia renal e na ativação do sistema renina-angiotensina intrarrenal.

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Estudo da estimulação crônica dos receptores β-adrenérgicos na função e morfologia renal e na ativação do sistema renina-angiotensina intrarrenal.