The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling
Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective i...
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| creator | Asker, Mervat E. Ali, Sousou I. Mohamed, Seham H. Abdelaleem, Rasha M.A. Younis, Nahla N. |
| description | Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage. |
| doi_str_mv | 10.1016/j.lfs.2021.119388 |
| format | Article |
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Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2021.119388</identifier><identifier>PMID: 33774028</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Anemia ; Animals ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; BM-MSCs ; Bone marrow ; Bone marrow transplantation ; Caspase-3 ; Combined Modality Therapy ; Combined treatment ; Creatinine ; Creatinine - blood ; Dosage ; Downstream effects ; Erythropoietin ; Erythropoietin - therapeutic use ; Erythropoietin receptor ; Fractionation ; Gamma irradiation ; Gamma Rays - adverse effects ; Glutathione ; Irradiation ; Kidney - radiation effects ; Kidney diseases ; Kidneys ; Male ; Malondialdehyde ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Nephropathy ; pAkt ; pJAK2 ; pPI3K ; Radiation damage ; Radiation dosage ; Radiation effects ; Radiation hazards ; Radiation injuries ; Radiation Injuries, Experimental - therapy ; Radiation therapy ; Rats ; Rats, Wistar ; Rodents ; Side effects ; Signaling ; Stem cell transplantation ; Stem cells ; Transplantation ; Urea ; Urea - blood ; γ Radiation ; γ-Irradiation</subject><ispartof>Life sciences (1973), 2021-06, Vol.275, p.119388, Article 119388</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier BV Jun 15, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-12d077986b6b56932f4542659cd7f7aa3ebfcc77c7aff809f3564568d528928e3</citedby><cites>FETCH-LOGICAL-c381t-12d077986b6b56932f4542659cd7f7aa3ebfcc77c7aff809f3564568d528928e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2021.119388$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33774028$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asker, Mervat E.</creatorcontrib><creatorcontrib>Ali, Sousou I.</creatorcontrib><creatorcontrib>Mohamed, Seham H.</creatorcontrib><creatorcontrib>Abdelaleem, Rasha M.A.</creatorcontrib><creatorcontrib>Younis, Nahla N.</creatorcontrib><title>The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Anemia</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BM-MSCs</subject><subject>Bone marrow</subject><subject>Bone marrow transplantation</subject><subject>Caspase-3</subject><subject>Combined Modality Therapy</subject><subject>Combined treatment</subject><subject>Creatinine</subject><subject>Creatinine - blood</subject><subject>Dosage</subject><subject>Downstream effects</subject><subject>Erythropoietin</subject><subject>Erythropoietin - therapeutic use</subject><subject>Erythropoietin receptor</subject><subject>Fractionation</subject><subject>Gamma irradiation</subject><subject>Gamma Rays - adverse effects</subject><subject>Glutathione</subject><subject>Irradiation</subject><subject>Kidney - radiation effects</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Male</subject><subject>Malondialdehyde</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mesenchymal stem cells</subject><subject>Nephropathy</subject><subject>pAkt</subject><subject>pJAK2</subject><subject>pPI3K</subject><subject>Radiation damage</subject><subject>Radiation dosage</subject><subject>Radiation effects</subject><subject>Radiation hazards</subject><subject>Radiation injuries</subject><subject>Radiation Injuries, Experimental - therapy</subject><subject>Radiation therapy</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Side effects</subject><subject>Signaling</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transplantation</subject><subject>Urea</subject><subject>Urea - blood</subject><subject>γ Radiation</subject><subject>γ-Irradiation</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuKFDEUhgtRnHb0AdxIwHX15FKppHQlgzcYEGRch1Ry0p22UmmT9Ei9ok9lim5duBACh3D-85_L1zQvCd4STPqbw3ZyeUsxJVtCBiblo2ZDpBha3DPyuNlgTLuWUcyvmmc5HzDGnAv2tLliTIgOU7lpft3vAYFz3mizoOjQGGdAQacUf7YWkn8AiwJkmM1-CXpCuUBABqYpIz3bm5gQpKXsUzxGD8XPqD4dYPIx6frdoe_ezrAgq4PewZrd6RA08ilp63Wp9lWY36CvcYJ1gDnO7R6CLhdH828DPRff6mM8lrhms9_NeqqdnjdPnJ4yvLjE6-bbh_f3t5_auy8fP9--u2sNk6S0hFosxCD7sR95PzDqOt7Rng_GCie0ZjA6Y4QwQjsn8eAY7zveS8upHKgEdt28PvseU_xxglzUIZ5SnSEryikhlQcWVUXOKpNizgmcOiZf77oogtVKTx1UpadWeupMr9a8ujifxgD2b8UfXFXw9iyAut-Dh6Sy8RUNWJ_AFGWj_4_9b9Cgr6A</recordid><startdate>20210615</startdate><enddate>20210615</enddate><creator>Asker, Mervat E.</creator><creator>Ali, Sousou I.</creator><creator>Mohamed, Seham H.</creator><creator>Abdelaleem, Rasha M.A.</creator><creator>Younis, Nahla N.</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20210615</creationdate><title>The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling</title><author>Asker, Mervat E. ; Ali, Sousou I. ; Mohamed, Seham H. ; Abdelaleem, Rasha M.A. ; Younis, Nahla N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-12d077986b6b56932f4542659cd7f7aa3ebfcc77c7aff809f3564568d528928e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Anemia</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>BM-MSCs</topic><topic>Bone marrow</topic><topic>Bone marrow transplantation</topic><topic>Caspase-3</topic><topic>Combined Modality Therapy</topic><topic>Combined treatment</topic><topic>Creatinine</topic><topic>Creatinine - blood</topic><topic>Dosage</topic><topic>Downstream effects</topic><topic>Erythropoietin</topic><topic>Erythropoietin - therapeutic use</topic><topic>Erythropoietin receptor</topic><topic>Fractionation</topic><topic>Gamma irradiation</topic><topic>Gamma Rays - adverse effects</topic><topic>Glutathione</topic><topic>Irradiation</topic><topic>Kidney - radiation effects</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Male</topic><topic>Malondialdehyde</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mesenchymal stem cells</topic><topic>Nephropathy</topic><topic>pAkt</topic><topic>pJAK2</topic><topic>pPI3K</topic><topic>Radiation damage</topic><topic>Radiation dosage</topic><topic>Radiation effects</topic><topic>Radiation hazards</topic><topic>Radiation injuries</topic><topic>Radiation Injuries, Experimental - therapy</topic><topic>Radiation therapy</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Side effects</topic><topic>Signaling</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transplantation</topic><topic>Urea</topic><topic>Urea - blood</topic><topic>γ Radiation</topic><topic>γ-Irradiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asker, Mervat E.</creatorcontrib><creatorcontrib>Ali, Sousou I.</creatorcontrib><creatorcontrib>Mohamed, Seham H.</creatorcontrib><creatorcontrib>Abdelaleem, Rasha M.A.</creatorcontrib><creatorcontrib>Younis, Nahla N.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Asker, Mervat E.</au><au>Ali, Sousou I.</au><au>Mohamed, Seham H.</au><au>Abdelaleem, Rasha M.A.</au><au>Younis, Nahla N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2021-06-15</date><risdate>2021</risdate><volume>275</volume><spage>119388</spage><pages>119388-</pages><artnum>119388</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Radiation-induced multiple organ injury, including γ-radiation nephropathy, is the most common. Even with dose fractionation strategy, residual late side effects are inevitable. Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation and erythropoietin (EPO) have shown to be effective in treating chronic kidney disease and associated anemia. This study aimed to evaluate the effect of BM-MSCs and/or EPO in fractionated γ-irradiation induced kidney damage in rats. Adult male Wistar rats were randomized into 2 groups; normal and 8 Gy (fractionated dose of 2 Gy for 4 days) γ-irradiated rats. Animal from both groups were subdivided to receive the following treatments: BM-MSCs (1 × 106 cells/rat, i.v - once), EPO (100 IU/kg, i.p - every other day for 30 days) or their combined treatment (BM-MSCs and EPO). γ-Irradiated rats showed a noticeable elevation in serum urea and creatinine, kidney malondialdehyde (MDA) and caspase 3 activity. They also revealed significant drop in kidney glutathione (GSH) and Bcl2 protein contents. Conspicuously, they revealed down-regulation of renal EPO signaling (EPO, EPOR, pJAK2, pPI3K and pAkt). Conversely, groups treated with BM-MSCs and/or EPO revealed significant modulation in most tested parameters and appeared to be effective in minimizing the hazard effects of radiation. In conclusion, BM-MSCs and/or EPO exhibited therapeutic potentials against nephrotoxicity induced by fractionated dose of γ-irradiation. An effect mediated by antioxidant and non-hematopoietic EPO downstream anti-apoptotic signaling (PI3K/Akt) pathway. EPO potentiate the repair capabilities of BM-MSCs making this combined treatment a promising therapeutic strategy to overcome radiotherapy-induced kidney damage.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33774028</pmid><doi>10.1016/j.lfs.2021.119388</doi></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Anemia Animals Antioxidants Apoptosis Apoptosis - drug effects BM-MSCs Bone marrow Bone marrow transplantation Caspase-3 Combined Modality Therapy Combined treatment Creatinine Creatinine - blood Dosage Downstream effects Erythropoietin Erythropoietin - therapeutic use Erythropoietin receptor Fractionation Gamma irradiation Gamma Rays - adverse effects Glutathione Irradiation Kidney - radiation effects Kidney diseases Kidneys Male Malondialdehyde Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Nephropathy pAkt pJAK2 pPI3K Radiation damage Radiation dosage Radiation effects Radiation hazards Radiation injuries Radiation Injuries, Experimental - therapy Radiation therapy Rats Rats, Wistar Rodents Side effects Signaling Stem cell transplantation Stem cells Transplantation Urea Urea - blood γ Radiation γ-Irradiation |
| title | The efficacy of bone marrow-derived mesenchymal stem cells and/or erythropoietin in ameliorating kidney damage in gamma irradiated rats: Role of non-hematopoietic erythropoietin anti-apoptotic signaling |
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