Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems
While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliora...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1209 |
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| author | Sajeev Wagle Hyun-Jaung Sim Govinda Bhattarai Ki-Choon Choi Sung-Ho Kook Jeong-Chae Lee Young-Mi Jeon |
| author_facet | Sajeev Wagle Hyun-Jaung Sim Govinda Bhattarai Ki-Choon Choi Sung-Ho Kook Jeong-Chae Lee Young-Mi Jeon |
| author_sort | Sajeev Wagle |
| collection | DOAJ |
| description | While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing ROS accumulation and oxidative stress is necessary for TBI-requiring clinical treatments. Here, we explored whether administration of ferulic acid, a dietary antioxidant, protects against TBI-mediated systemic damages, and examined the possible mechanisms therein. Sublethal TBI (5 Gy) decreased body growth, lifespan, and production of circulating blood cells in mice, together with ROS accumulation, and senescence induction of BM-conserved HSCs and MSCs. TBI also impaired BM microenvironment and bone mass accrual, which was accompanied by downregulated osteogenesis and by osteoclastogenic and adipogenic activation in BM. Long-term intraperitoneal injection of ferulic acid (50 mg/kg body weight, once per day for 37 consecutive days) protected mice from TBI-mediated mortality, stem cell senescence, and bone mass loss by restoring TBI-stimulated disorders in osteogenic, osteoclastic, and adipogenic activation in BM. In vitro experiments using BM stromal cells supported radioprotective effects of ferulic acid on TBI-mediated defects in proliferation and osteogenic differentiation. Overall, treatment with ferulic acid prevented TBI-mediated liver damage and enhanced endogenous antioxidant defense systems in the liver and BM. Collectively, these results support an efficient protection of TBI-mediated systemic defects by supplemental ferulic acid, indicating its clinical usefulness for TBI-required patients. |
| first_indexed | 2024-03-10T09:03:39Z |
| format | Article |
| id | doaj.art-be55ca7b15e8448191f37301b6668e87 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:39Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-be55ca7b15e8448191f37301b6668e872023-11-22T06:35:43ZengMDPI AGAntioxidants2076-39212021-07-01108120910.3390/antiox10081209Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense SystemsSajeev Wagle0Hyun-Jaung Sim1Govinda Bhattarai2Ki-Choon Choi3Sung-Ho Kook4Jeong-Chae Lee5Young-Mi Jeon6Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaGrassland and Forages Research Center, National Institute of Animal Science, Cheonan 31002, KoreaCluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaCluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, Jeonbuk National University School of Dentistry, Jeonju 54896, KoreaWhile total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing ROS accumulation and oxidative stress is necessary for TBI-requiring clinical treatments. Here, we explored whether administration of ferulic acid, a dietary antioxidant, protects against TBI-mediated systemic damages, and examined the possible mechanisms therein. Sublethal TBI (5 Gy) decreased body growth, lifespan, and production of circulating blood cells in mice, together with ROS accumulation, and senescence induction of BM-conserved HSCs and MSCs. TBI also impaired BM microenvironment and bone mass accrual, which was accompanied by downregulated osteogenesis and by osteoclastogenic and adipogenic activation in BM. Long-term intraperitoneal injection of ferulic acid (50 mg/kg body weight, once per day for 37 consecutive days) protected mice from TBI-mediated mortality, stem cell senescence, and bone mass loss by restoring TBI-stimulated disorders in osteogenic, osteoclastic, and adipogenic activation in BM. In vitro experiments using BM stromal cells supported radioprotective effects of ferulic acid on TBI-mediated defects in proliferation and osteogenic differentiation. Overall, treatment with ferulic acid prevented TBI-mediated liver damage and enhanced endogenous antioxidant defense systems in the liver and BM. Collectively, these results support an efficient protection of TBI-mediated systemic defects by supplemental ferulic acid, indicating its clinical usefulness for TBI-required patients.https://www.mdpi.com/2076-3921/10/8/1209ferulic acidtotal body irradiationbone marrow microenvironmentstem cell senescencebone marrow injuryreactive oxygen species |
| spellingShingle | Sajeev Wagle Hyun-Jaung Sim Govinda Bhattarai Ki-Choon Choi Sung-Ho Kook Jeong-Chae Lee Young-Mi Jeon Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems Antioxidants ferulic acid total body irradiation bone marrow microenvironment stem cell senescence bone marrow injury reactive oxygen species |
| title | Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems |
| title_full | Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems |
| title_fullStr | Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems |
| title_full_unstemmed | Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems |
| title_short | Supplemental Ferulic Acid Inhibits Total Body Irradiation-Mediated Bone Marrow Damage, Bone Mass Loss, Stem Cell Senescence, and Hematopoietic Defect in Mice by Enhancing Antioxidant Defense Systems |
| title_sort | supplemental ferulic acid inhibits total body irradiation mediated bone marrow damage bone mass loss stem cell senescence and hematopoietic defect in mice by enhancing antioxidant defense systems |
| topic | ferulic acid total body irradiation bone marrow microenvironment stem cell senescence bone marrow injury reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/10/8/1209 |
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