Apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries

Imam, Faisal; Al-Harbi, Naif O.; Alharbi, Mohammed; Qamar, Wajhul; Aljerian, Khaldoon; Belali, Osamah M; Alsanea, Sary; Alanazi, Ahmed Z.; Alhazzani, Khalid

doi:10.1016/j.intimp.2018.11.023

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…Several investigators reported significantly reduced activities of SOD, CAT, GPx, GST and GSH in cancer-bearing animals with elevated free radicals and various humoral and cellular mediators. Multiple researchers have recorded substantially lower GST, CAT, GSH, Gpx, and SOD activity in carcinogenic animals with high free radicals and certain humoral factors. , Lower respiratory tract glutathione and related enzymes can be the first line of defense for lung injury in the epithelial body. , …”

Section: Resultsmentioning

confidence: 99%

Anticancer Effect of Rosiglitazone, a PPAR-γ Agonist against Diethylnitrosamine-Induced Lung Carcinogenesis

Wu¹,

Sreeharsha

Sharma

et al. 2020

ACS Omega

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Multiple effects on cancer cells are exerted by the peroxisome proliferator-activated receptor γ (PPAR-γ). Recent studies have shown that rosiglitazone, a synthetic PPAR-γ ligand, inhibits the growth of cells. This research was designed to assess the impact of rosiglitazone on diethylnitrosamine (DENA)-induced lung carcinogenesis in Wistar rats and to study the underlying molecular mechanism. A total of 40 adult male Wistar rats were separated into four groups as follows: group 1 is known as a control. Group 2 is known as the DENA group (150 mg/ kg, i.p.). Group 3 and group 4 denote DENA-induced rats treated with 5 and 10 mg/kg rosiglitazone, respectively. Lipid peroxidation, various antioxidant enzymes, histological perceptions, and caspase-3, Bcl2, and Bax gene expression were measured in lung tissues. Rosiglitazone treatment reverted the DENA-induced changes in the expression of these genes, inflammatory cytokines, and oxidative stress. However, blotting analysis discovered reduced caspase-3 and BAX expressions and elevated Bcl-2 expression in DENA-induced rats. The expression of such proteins causing DENA lung cancer was restored by rosiglitazone therapy.

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Section: Resultsmentioning

confidence: 99%

Anticancer Effect of Rosiglitazone, a PPAR-γ Agonist against Diethylnitrosamine-Induced Lung Carcinogenesis

Wu¹,

Sreeharsha

Sharma

et al. 2020

ACS Omega

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“…Moreover, phosphodiesterase (PDE)-4 inhibition by apremilast extensively hindered activation of numerous pathways such as MAPK, NF-κB, and phosphatidylinositol-3-kinase-mTOR pathways, which are implicated in the regulation of both innate and adaptive immunity [ 79 ]. Indeed, the promising anti-inflammatory properties of apremilast conferred protection against carfilzomib-induced pulmonary and vascular injuries [ 80 ]. Taken together, the anti-inflammatory and immunomodulatory effects of apremilast could have therapeutic potential in the management of Covid-19.…”

Section: Drugs That Might Affect the Cytokines Storm In Covid-19mentioning

confidence: 99%

Promising drug repurposing approach targeted for cytokine storm implicated in SARS-CoV-2 complications

Shawki

Elsayed

Mantawy

et al. 2021

Immunopharmacology and Immunotoxicology

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A global threat has emerged in 2019 due to the rapid spread of Coronavirus disease (COVID-19). As of January 2021, the number of cases worldwide reached 103 million cases and 2.22 million deaths which were confirmed as the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This global pandemic galvanized the scientific community to study the causative virus (SARS-CoV2) pathogenesis, transmission, and clinical symptoms. Remarkably, the most common complication associated with this disease is the cytokine storm which is responsible for COVID-19 mortality. Thus, targeting the cytokine storm with new medications is needed to hamper COVID-19 complications where the most prominent strategy for the treatment is drug repurposing. Through this strategy, several steps are skipped especially those required for testing drug safety and thus may help in reducing the dissemination of this pandemic. Accordingly, the aim of this review is to outline the pathogenesis, clinical features, and immune complications of SARS-CoV2 in addition to suggesting several repurposed drugs with their plausible mechanism of action for possible management of severe COVID-19 cases.

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“…A series of studies show that Apremilast could ameliorate drug-induced cardiovascular toxicity by the inhibition of the ERK and JNK kinases, and NF-κB/inflammatory pathways [38][39]. Particularly, Apremilast acts to inhibit the NF-κB pathway by upregulating IL10 and downregulating TNF-α [40]. PDE4 inhibition causes intracellular accumulation of cAMP-responsive element-binding protein (CREB/ATF-1) family of transcription factors.…”

Section: Severementioning

confidence: 99%

Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells

Jia

Chen

Sun

2021

Aging

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Background and purpose: Skin tissue is the natural barrier that protects our body, the damage of which can be repaired by the epidermal stem cells (ESCs). However, external factors abolish the self-repair ability of ESCs by inducing oxidative stress and severe inflammation. Apremilast is a small molecular inhibitor of phosphodiesterase 4 that was approved for the treatment of psoriasis. In the present study, the protective property of Apremilast against IL-1α-induced dysfunction on epidermal stem cells, as well as the preliminary mechanism, will be investigated. Methods: ESCs were isolated from neonatal mice. The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. MitoSOX Red assay was used to determine the level of mitochondrial reactive oxygen species (ROS). Western blot and real-time PCR were utilized to determine the expression levels of IL-1R1, Myd88, and TRAF6. Activation of NF-κB was assessed by measuring the p-NF-κB p65 and luciferase activity. Capacities of ESCs were evaluated by measuring the gene expressions of integrin β1 and Krt19 using real-time PCR. Results: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. Subsequently, we found that the activated Myd88/TRAF6/NF-κB signaling pathway induced by stimulation with IL-1α was significantly inhibited by the introduction of Apremilast. As a result, Apremilast protected ESCs against IL-1α-induced impairment in capacities of ESCs, this was verified by the elevated expression levels of integrin β1 and Krt19. Conclusions: Apremilast might ameliorate IL-1α-induced dysfunction in ESCs by mitigating oxidative stress and inflammation through inhibiting the activation of the Myd88/TRAF6/NF-κB signaling pathway.

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Apremilast ameliorates carfilzomib-induced pulmonary inflammation and vascular injuries

Cited by 15 publications

References 28 publications

Anticancer Effect of Rosiglitazone, a PPAR-γ Agonist against Diethylnitrosamine-Induced Lung Carcinogenesis

Anticancer Effect of Rosiglitazone, a PPAR-γ Agonist against Diethylnitrosamine-Induced Lung Carcinogenesis

Promising drug repurposing approach targeted for cytokine storm implicated in SARS-CoV-2 complications

Apremilast ameliorates IL-1α-induced dysfunction in epidermal stem cells

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