Apremilast prevent doxorubicin-induced apoptosis and inflammation in heart through inhibition of oxidative stress mediated activation of NF-κB signaling pathways

Imam, Faisal; Al-Harbi, Naif O.; Al-Harbi, M. M.; Ansari, Mushtaq A.; Alasmari, Abdullah F.; Ansari, Mohd Nazam; Alanazi, Wael A.; Bahashwan, Saleh; Almutairi, Mashal M.; Alshammari, Musaad A.; Khan, Mohammad Rashid; Alsaad, Abdulaziz M.S.; Alotaibi, Moureq R.

doi:10.1016/j.pharep.2018.03.009

Cited by 52 publications

(48 citation statements)

References 61 publications

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“…Apremilast also contributes to restore endothelial disfunction, limiting cardiovascular disease risk 21,22 . Moreover, the molecule demonstrated to be an excellent metabolic regulator acting also on atherosclerotic plaque stabilization, blocking its progression 23 . Indeed, PDE4D is identified as a susceptible gene for ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers

Mazzilli

Lanna

Chiaramonte

et al. 2020

The Journal of Dermatology

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Psoriasis is a common inflammatory skin condition, affecting 2-4% of the worldwide population. Psoriasis remains an important public health challenge because there are many clinical forms of psoriasis in particular sites, probably related to the dysregulation of different cytokines. Therefore, there is a continuous need to improve treatment options with mechanisms of action different from those of the currently known therapies. Advances in knowledge of the molecular bases of pathogenesis lead to a better understanding of the disease, thus influencing the development and management of effective treatments. Moreover, data from recent published work indicate that psoriasis coexists with cardiovascular diseases, metabolic syndrome, diabetes mellitus and psychiatric disorders. We present results from our 52-week open-label trial in a cohort of psoriatic and psoriatic arthritis patients treated with daily p.o. doses of apremilast 60 mg. We confirmed the efficacy and safety of the drug in favoring the improvement of skin and joint disease as well as the modulation of metabolic biomarkers in diabetic and non-diabetic psoriatic patients. Apremilast could be used successfully in psoriatic patients affected by cardiometabolic comorbidities, ensuring an improvement in both diseases.

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Section: Discussionmentioning

confidence: 99%

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers

Mazzilli

Lanna

Chiaramonte

et al. 2020

The Journal of Dermatology

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“…The data are shown as the fold change in mRNA expression levels normalized to β-actin as a loading control. Cardiac proteins were extracted using lysis buffer as described before [23]. Brie y, cardiac tissue was minced and homogenized in ice-cold lysis buffer mixed with a protease inhibitor cocktail.…”

Section: Real-time Quantitative Polymerase Chain Reaction (Rt-pcr) Assaymentioning

confidence: 99%

“…After lysate collection, protein concentration was identi ed using the Direct Detect ® spectrometer (EMD Millipore, USA). The western blot technique was used to determine protein expression as described in our previous study [23]. We analyzed 25-50 μg on a 10% SDS-polyacrylamide gel electrophoresis (SDS-PAGE) for protein separation.…”

Section: Real-time Quantitative Polymerase Chain Reaction (Rt-pcr) Assaymentioning

confidence: 99%

Role of carnitine in regulation of hypoglycemia-induced hypertension and cardiac hypertrophy

Alanazi¹,

Al-Harbi²,

Imam³

et al. 2020

Preprint

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Background: Cardiovascular disease is a leading cause of death in diabetic patients. Hyperglycemia and iatrogenic hypoglycemia exacerbate several pathogenic mechanisms underlying hypertension and heart diseases. Carnitine is a potent endogenous antioxidant and cellular fatty acid transporter for antioxidative stress and energy production in the cardiovascular system. In the present study, we aimed to find the role of carnitine in the regulation of hypoglycemia-induced hypertension and cardiac hypertrophy. Methods: Albino Wistar male rats were divided into six groups. The, first three groups received saline (n= 5), D-carnitine (n= 5) at dose of 500mg/kg/day, intraperitoneal for carnitine depletion, or acetyl-L-carnitine (n= 5) at a dose of 300mg/kg/day, intraperitoneal for carnitine supplementation for 15 days. In the last three groups, rats had pretreatment conditions for 5 days with saline, D-carnitine or acetyl-L-carnitine. Then, they were treated with insulin glargine (InG) for 10 days with saline (n= 6), D-carnitine (n= 5) or acetyl-L-carnitine (n= 6), respectively. Results: Our results showed that carnitine deficiency provoked hypoglycemia-induced hypertension. Mean arterial pressure was elevated from 78.16 ± 4.67 to 100 ± 2.09 mmHg in InG treated group, and from 78.2 ± 3.8 to 123.4 ± 12.6 mmHg in InG+D-carnitine treated group. Acetyl-L-carnitine resisted the elevation in blood pressure in all hypoglycemic animals and kept it within the normal values (68.33 ± 6.7 mmHg). In heart, acetyl-L-carnitine increased myocardial carnitine content leading to the attenuation of hypoglycemia-induced oxidative stress, which was evaluated through measurement of the oxidative stress biomarkers such as inducible nitric oxide synthase, NAD(P)H quinone dehydrogenase-1, heme oxygenase-I, and glutathione transferase. Moreover, acetyl-L-carnitine prevented induction of cardiac hypertrophy during hypoglycemic conditions, which was assessed via the evaluation of mRNA expression of the cardiac hypertrophy biomarkers, α-myosin heavy chain and β-myosin heavy chain. Conclusions: These findings demonstrate that carnitine plays an essential role in providing energy and antioxidants to the cardiovascular system leading to the prevention of hypoglycemia-induced hypertension and cardiac hypertrophy.

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“…Inflammatory response is widely implicated in multiple cellular processes, such as proliferation, apoptosis and differentiation . It is reported inflammation is significantly associated with osteogenic differentiation of MSCs.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] Inflammatory response is widely implicated in multiple cellular processes, such as proliferation, apoptosis and differentiation. [13][14][15][16][17] It is reported inflammation is significantly associated with osteogenic differentiation of MSCs. Furthermore, as is widely accepted that activation of inflammatory response has an inhibitory effect on osteogenesis.…”

mentioning

confidence: 99%

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

Zhu

et al. 2018

J Cellular Molecular Medi

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As is previously reported, mesenchymal stem cells have potential ability to differentiate into osteocytes. However, the underlying mechanism during this biological process is poorly understood. In the present study, we identify a novel long non‐coding RNA named HOXA‐AS2 as a critical regulator during the formation of osteogenesis. Attenuation of HOXA‐AS2 can reduce the calcium deposition and repress the alkaline phosphatase activity. Moreover, the expressions of osteogenic marker genes are markedly downregulated after HOXA‐AS2 depletion. Mechanistically, we found HOXA‐AS2 can regulate the transcriptional activity of NF‐κB, a critical inhibitor of osteogenesis. More importantly, HOXA‐AS2 knockdown could result in the transcriptional repression of the osteogenic master transcription factor SP7 by a NF‐κB/HDAC2‐coordinated H3K27 deacetylation mechanism. Based on these studies, we conclude that HOXA‐AS2 may serve as a promising therapeutic target for bone tissue repair and regeneration in the near future.

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Apremilast prevent doxorubicin-induced apoptosis and inflammation in heart through inhibition of oxidative stress mediated activation of NF-κB signaling pathways

Abstract: These findings suggested that apremilast can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress mediated activation of nuclear factor-kappa B signaling pathways.

Cited by 52 publications

References 61 publications

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers

Real life experience of apremilast in psoriasis and arthritis psoriatic patients: Preliminary results on metabolic biomarkers

Role of carnitine in regulation of hypoglycemia-induced hypertension and cardiac hypertrophy

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

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