PUBLICATION
Regular Supplementation with Antioxidants Rescues Doxorubicin-Induced Bone Deformities and Mineralization Delay in Zebrafish
- Authors
- Poudel, S., Martins, G., Cancela, M.L., Gavaia, P.J.
- ID
- ZDB-PUB-221212-15
- Date
- 2022
- Source
- Nutrients 14(23): (Journal)
- Registered Authors
- Cancela, Leonor
- Keywords
- MitoTEMPO, doxorubicin, oxidative stress, resveratrol, secondary osteoporosis, zebrafish
- MeSH Terms
-
- Animals
- Antioxidants*/metabolism
- Doxorubicin/toxicity
- Lipid Peroxidation
- Oxidative Stress
- Reactive Oxygen Species/metabolism
- Zebrafish*
- PubMed
- 36500990 Full text @ Nutrients
Citation
Poudel, S., Martins, G., Cancela, M.L., Gavaia, P.J. (2022) Regular Supplementation with Antioxidants Rescues Doxorubicin-Induced Bone Deformities and Mineralization Delay in Zebrafish. Nutrients. 14(23):.
Abstract
Osteoporosis is characterized by an abnormal bone structure with low bone mass and degradation of microarchitecture. Oxidative stress induces imbalances in osteoblast and osteoclast activity, leading to bone degradation, a primary cause of secondary osteoporosis. Doxorubicin (DOX) is a widely used chemotherapy drug for treating cancer, known to induce secondary osteoporosis. The mechanism underlying DOX-induced bone loss is still not fully understood, but one of the relevant mechanisms is through a massive accumulation of reactive oxygen and nitrogen species (i.e., ROS and NOS) leading to oxidative stress. We investigated the effects of antioxidants Resveratrol and MitoTEMPO on DOX-induced bone impairment using the zebrafish model. DOX was shown to increase mortality, promote skeletal deformities, induce alterations on intestinal villi, impair growth and mineralization and significantly downregulate osteoblast differentiation markers osteocalcin 2 and osterix/sp7. Lipid peroxidation was significantly increased in DOX-supplemented groups as compared to control and antioxidants, suggesting ROS formation as one of the key factors for DOX-induced bone loss. Furthermore, DOX affected mineral contents, suggesting an altered mineral metabolism. However, upon supplementation with antioxidants, DOX-induced effects on mineral content were rescued. Our data show that supplementation with antioxidants effectively improves the overall growth and mineralization in zebrafish and counteracts DOX-induced bone anomalies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping