Association of Superoxide‐Induced Oxidative Stress With Rotator Cuff Tears in Human Patients

Yoshida, Koichiro; Itoigawa, Yoshiaki; Wada, Tomoki; Maruyama, Yoshihiro; Nojiri, Hidetoshi; Kawasaki, Takayuki

doi:10.1002/jor.24472

Cited by 22 publications

(26 citation statements)

References 51 publications

(111 reference statements)

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“…ROS are short-lived molecules, which makes them difficult to be directly measured in vivo. Thus, we and other researchers have used dihydroethidium (DHE) staining to visualize ROS levels in freshly frozen tissue sections 35 , 40 . Figure 7 a shows that the DHE fluorescence intensities were significantly elevated in mouse heart tissues collected on day 3, 4 and 7 after TBI, and returned to similar level as sham-irradiated on day-14.…”

Section: Resultsmentioning

confidence: 99%

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IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

Cui

Hull

et al. 2020

Sci Rep

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Recent studies suggested that radiation exposure causes local and systemic inflammatory responses and induces cell and tissue damage. We have reported that IL-18 plays an important role in radiation-induced injury. Here, we demonstrate that IL-18 binding protein (IL-18BP), a natural antagonist of IL-18, was significantly increased (1.7–63 fold) in mouse serum on day 1 after 0.5–10 Gy TBI. However, this high level of IL-18BP was not sufficient to neutralize the active IL-18 in irradiated mice, resulting in a radiation dose-dependent free IL-18 increase in these mice’s serum which led to pathological alterations to the irradiated cells and tissues and finally caused animal death. Administration of recombinant human (rh) IL-18BP (1.5 mg/kg) with single (24, 48 or 72 h post-TBI) or double doses (48 h and 5 days post-TBI) subcutaneous (SC) injection increased 30-day survival of CD2F1 mice after 9 Gy TBI 12.5–25% compared with the vehicle control treated group, respectively. Furthermore, the mitigative effects of rhIL-18BP included balancing the ratio of IL-18/IL-18BP and decreasing the free IL-18 levels in irradiated mouse serum and significantly increasing blood cell counts, BM hematopoietic cellularity and stem and progenitor cell clonogenicity in mouse BM. Furthermore, IL-18BP treatment inhibited the IL-18 downstream target interferon (IFN)-γ expression in mouse BM, decreased reactive oxygen species (ROS) level in the irradiated mouse heart tissues, attenuated the stress responsive factor GDF-15 (growth differentiation factor-15) and increased the intestine protector citrulline level in total body irradiated mouse serum, implicating that IL-18BP may protect multiple organs from radiation-induced inflammation and oxidative stress. Our data suggest that IL-18 plays a key role in radiation-induced cell and tissue damage and dysfunction; and for the first time demonstrated that IL-18BP counters IL-18 activation and therefore may mitigate/treat radiation-induced multiple organ injuries and increase animal survival with a wider therapeutic window from 24 h and beyond after lethal doses of radiation exposure.

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Section: Resultsmentioning

confidence: 99%

“…ROS are short-lived molecules, which makes them difficult to be directly measured in vivo. In this study, we used DHE staining to visualize ROS levels in freshly frozen heart tissue sections based on our and others’ reports 35 , 40 . We acknowledge this limitation when interpreting our findings.…”

Section: Discussionmentioning

confidence: 99%

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

Cui

Hull

et al. 2020

Sci Rep

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“…The protocol of the experiment was based on a previous study. 52 The DHE (Life Technologies Corporation) was adjusted to 10 mmol/L and applied to cover the entire section on the slide. After the sections on the slides were incubated in a chamber at 37°C for 30 minutes, they were washed twice using phosphate-buffered saline and enclosed with a cover glass.…”

Section: Dhe Fluorescence Intensity For Evaluation Of Oxidative Stressmentioning

confidence: 99%

“…11,19 Superoxide dismutase (SOD) is a major antioxidant enzyme that reduces the levels of reactive oxygen species in vivo. 33,34 Morikawa et al 36,37 demonstrated that rotator cuff degeneration was associated with excess oxidative stress in SOD1-deficient mice (SOD1 is 1 of 3 SOD isoforms that have different active centers and localities), and Yoshida et al 52 reported that imbalance of oxidative stress was implicated in the degeneration of rotator cuffs in patients with rotator cuff tears. However, it is unclear whether oxidative stress contributes to recurrent tear after ARCR.…”

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confidence: 99%

Association of Recurrent Tear After Arthroscopic Rotator Cuff Repair and Superoxide-Induced Oxidative Stress

et al. 2021

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Background: Recurrent tears after arthroscopic rotator cuff repair (ARCR) remain a significant clinical problem. Oxidative stress contributes to the degeneration of the rotator cuff, and a degenerative rotator cuff can lead to recurrent tear after ARCR. However, the correlation between oxidative stress and retear after ARCR is unclear. Purpose: To investigate the correlation between superoxide-induced oxidative stress and recurrent tear after ARCR. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 68 patients who underwent ARCR using a suture-bridge technique participated in this study. Specimens were collected from the edge of the torn tendon during surgery. The modified Bonar score was used to evaluate degeneration of the rotator cuff on histological specimens, and fluorescence intensity on dihydroethidium (DHE) staining was used to detect oxidative stress. Superoxide dismutase (SOD) enzyme activity was also measured. The following were used for clinical evaluation: age, tear size on magnetic resonance imaging (MRI) before surgery, Goutallier classification on MRI before surgery, and Japanese Orthopaedic Association score before and 6 months after surgery. After the repaired rotator cuffs were evaluated on MRI 6 months after surgery, the patients were divided into groups: those with a healed rotator cuff (healed group; n = 46) and those with a recurrent tear (retear group; n = 22). The significant differences between the groups were determined with regard to clinical evaluation, modified Bonar score, DHE intensity, and SOD activity. In addition, multivariate logistic regression analysis was performed to investigate risk factors for recurrent tear. Results: Age, tear size, Goutallier classification, modified Bonar score, DHE intensity, and SOD activity were significantly greater in the retear group than in the healed group, although the Japanese Orthopaedic Association score was not significantly different. Multiple logistic regression analysis demonstrated that age, tear size, and SOD activity were significantly correlated with recurrent tear. Conclusion: In addition to tear size and age, superoxide-induced oxidative stress may be an exacerbating factor for retear after ARCR.

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“…In vitro models are used to examine how dexamethasone can protect the tendon from degeneration, the roles of substrate stiffness and pulsed electromagnetic fields in tendon responses to inflammation, and tendon responses to mechanical loading . Finally, a series of papers examines the risk factors and susceptibility for rotator cuff disease and injury and the use of imaging modalities to assess changes to the cuff after repair . This special issue demonstrates exciting progress in the field towards understanding tendon pathogenesis and healing and presents a number of novel strategies to prevent disease progression and improve healing.…”

mentioning

confidence: 99%

Discovery to delivery in tendon research

Derwin

Thomopoulos

2019

Journal Orthopaedic Research

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Association of Superoxide‐Induced Oxidative Stress With Rotator Cuff Tears in Human Patients

Cited by 22 publications

References 51 publications

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

IL-18 binding protein (IL-18BP) as a novel radiation countermeasure after radiation exposure in mice

Association of Recurrent Tear After Arthroscopic Rotator Cuff Repair and Superoxide-Induced Oxidative Stress

Discovery to delivery in tendon research

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