A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories
| العنوان: | A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories |
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| المؤلفون: | Rehab A. Hasan, Manal L. Louka, Maggie M. Ramzy, Ghada A. Abdel-Latif, Mona F. Schaalan, Noura F. Elmongy, Azza H. Abd Elwahab |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-17 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Angiotensin receptor, MAP Kinase Signaling System, NF-E2-Related Factor 2, Tetrazoles, lcsh:Medicine, Pharmacology, Lung injury, Predictive markers, Protective Agents, medicine.disease_cause, Article, Antioxidants, Sacubitril, Leukocyte Count, Fibrosis, Natriuretic Peptide, Brain, NAD(P)H Dehydrogenase (Quinone), medicine, Animals, Phosphorylation, lcsh:Science, Analytical biochemistry, Cyclophosphamide, Lung, Neprilysin, Multidisciplinary, L-Lactate Dehydrogenase, Chemistry, Aminobutyrates, Biphenyl Compounds, lcsh:R, NF-kappa B, Lung Injury, Translational research, medicine.disease, Rats, Drug Combinations, MicroRNAs, Gene Expression Regulation, Valsartan, Cytokines, lcsh:Q, Inflammation Mediators, Bronchoalveolar Lavage Fluid, Heme Oxygenase-1, Sacubitril, Valsartan, Oxidative stress, medicine.drug |
| الوصف: | Cyclophosphamide (CP) is a chemotherapeutic agent that induces oxidative stress causing multiple organ damage. Sacubitril/valsartan, is a combined formulation of neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (valsartan), that induces the protective effect of brain natriuretic peptide. The aim of the current study is to investigate the prophylactic impacts of sacubitril/valsartan versus valsartan against CP-induced lung toxicity in rats. Rats were assigned randomly into 6 groups; control; received corn oil (2 ml/kg/day; p.o. for 6 days), sacubitril/valsartan (30 mg/kg; p.o. for 6 days), valsartan (15 mg/kg; p.o. for 6 days), CP (200 mg/kg; i.p. on day 5), sacubitril/valsartan + CP (30 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively), valsartan + CP (15 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively). Both sacubitril/valsartan and valsartan produced a significant decrease in the inflammation and fibrosis markers in the BALF, in comparison with the CP group. Both sacubitril/valsartan and valsartan produced an apparent decrease in the relative genes expression of miR-150-3p and NF-κB, as well as a significant decrease in the relative expression of P38 and ERK1/2 MAPKs and an increase in the relative gene expression of Nrf-2, compared to CP group. Intriguingly, sacubitril/valsartan , showed subtle superiority in almost all investigated parameters, compared to valsartan. In conclusion, sacubitril/valsartan effectively abrogated the CP induced lung inflammation and fibrosis, providing a potential promising protection that could be linked to their ability to inhibit miR-150-3p via inhibition of NF-κB and MAPK signaling pathways. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77a5e8ee3226757eb0f710cdba7bf7acTest http://link.springer.com/article/10.1038/s41598-020-69810-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....77a5e8ee3226757eb0f710cdba7bf7ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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