Journal article
Targeting Oxidative Stress with Amobarbital to Prevent Intervertebral Disc Degeneration: Part II. Rabbit Disc Herniation Model
The spine journal, Vol.26(5), pp.1048-1058
05/2026
DOI: 10.1016/j.spinee.2025.12.003
PMID: 41397569
Abstract
Evidence that oxidative stress contributes to the progression of post-traumatic intervertebral disc degeneration suggests targeting oxidant metabolism in disc cells as a strategy to mitigate degeneration in injured discs. We previously identified amobarbital, a drug that suppresses mitochondrial activity in a cell culture model with the chemical induction of oxidative stress, as a promising candidate for this purpose.
The objective of this study was to investigate the preventive effects of amobarbital on the progression of disc degeneration using a rabbit disc herniation model.
The effects of amobarbital on the prevention of disc degeneration were evaluated in both ex vivo and in vivo herniated discs.
Spine motion segments or animals were randomly assigned for intact control, vehicle control (hydrogel only), and amobarbital. Disc herniation was initiated by puncturing the annulus fibrosus with a needle, and amobarbital was delivered to the nucleus pulposus in a Pluronic® F-127/hyaluronic acid (HA) hydrogel. A modified histological classification was applied to evaluate for degenerative cellular and matrix changes in both the annulus fibrosus and nucleus pulposus. Additionally, immunohistochemical staining for apoptosis and oxidative stress response, and radiography for disc height index were examined in the ex vivo and in vivo models, respectively.
Amobarbital injection allowed uniform distribution in the whole nucleus pulposus and showed sustained release for 3-4 days. In an organ culture model, amobarbital treatment after a discal injury prohibited morphologic changes of notochordal cells, structural changes of extracellular matrix, endplate chondrocyte migration, and cell apoptosis compared with the vehicle control. Similarly, the preventive effects of amobarbital on disc degeneration were confirmed in an animal study, especially at 2 weeks, with maintained disc height.
In summary, amobarbital injection loaded in F127/HA hydrogel reduced cellular and structural degenerative changes against herniated discal injuries. Therefore, amobarbital has great potential for treating degenerative disc degeneration.
Amobarbital encapsulated in hydrogel in this model allowed for effective local delivery into the nucleus pulposus and sustained release of amobarbital, which is promising for potential clinical application. Delivering amobarbital in nucleus pulposus cells may be a therapeutic option to retard intervertebral disc degeneration.
Details
- Title: Subtitle
- Targeting Oxidative Stress with Amobarbital to Prevent Intervertebral Disc Degeneration: Part II. Rabbit Disc Herniation Model
- Creators
- Venkateswaran Ganesh - University of IowaDouglas C Fredericks - University of IowaMitchell C Coleman - University of IowaEmily B Petersen - University of IowaYoussef W Naguib - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsJordon D Turner - University of IowaJaison Marks - University of IowaJames A Martin - University of IowaAliasger K Salem - University of IowaTae-Hong Lim - University of IowaDongrim Seol - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The spine journal, Vol.26(5), pp.1048-1058
- DOI
- 10.1016/j.spinee.2025.12.003
- PMID
- 41397569
- NLM abbreviation
- Spine J
- ISSN
- 1878-1632
- eISSN
- 1878-1632
- Publisher
- Elsevier
- Grant note
- U.S. Army Medical Research Acquisition Activity, Chandler Street, Fort Detrick: MD 21702-5014 Assistant Secretary of Defense for Health Affairs by the Department of Defense: W81XWH2010152
The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014, is the awarding and administering acquisition office. This work was supported by the Assistant Secretary of Defense for Health Affairs, endorsed by the Department of Defense, through the Peer Reviewed Medical Research Program under award no. W81XWH2010152. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense. In conducting research using animals, the investigators adhere to the laws of the United States and regulations of the Department of Agriculture. The authors declare that there is a potential intellectual property regarding the publication of this article. The authors thank BHRL/ISRL-ARS and OHSC staffs for the animal surgical and histological processes, Anupam Tiwari (AT) for histological grading, and Abigail Smith and Jaycie O'Neill for invaluable administrative and technical support.
- Language
- English
- Electronic publication date
- 12/13/2025
- Date published
- 05/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9985090654002771
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