Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

Fleckenstein, Katharina; Zgonjanin, Larisa; Chen, Liguang; Rabbani, Zahid N.; Jackson, Isabel L.; Thrasher, Bradley A.; Kirkpatrick, John P.; Foster, W. Michael; Vujašković, Željko

doi:10.1016/j.ijrobp.2006.12.056

Cited by 132 publications

(154 citation statements)

References 39 publications

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“…It may also be important that inflammatory cells can produce several orders of magnitude more ROS than would be produced directly by radiation doses of the size we are using [170,172]. Thus the levels of genistein used in the current studies may be sufficient to reduce intracellular ROS (RNOS) to low levels but may be insufficient to do this for extracellular ROS produced by the induced inflammatory response.…”

Section: Control Dietmentioning

confidence: 99%

“…There are at least three potential sources of ROS within the irradiated lung, first that which is produced as a direct result of radiation, second that is generated by inflammatory cells [12,170], and third from the mitochondria because of leakage from the electron transport chain [14]. Using whole lung irradiation it is difficult to distinguish between these sources; however, previous studies in our lab using half lung irradiation of rats [27, 28, 119] showed significant DNA damage both in and out of the radiation field.…”

Section: Control Dietmentioning

confidence: 99%

“…angiotensin II furthering inflammatory cell recruitment [170]. All of these possibilities suggest that the use of higher doses of genistein may be required to achieve significant effects on functional deficits following lung irradiation.…”

Section: Control Dietmentioning

confidence: 99%

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Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.ii Acknowledgements

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Section: Control Dietmentioning

confidence: 99%

Section: Control Dietmentioning

confidence: 99%

See 1 more Smart Citation

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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show abstract

“…12 mm lead blocks were used to protect the left thorax and the rest of the body. This is a prerequisite for studying long-term changes (months, [5,6,11,13]) after RT which might not be tolerated by the animals if both lungs were irradiated with 28 Gy, a dose necessary to induce a robust fibrotic damage in the lung.…”

Section: Irradiation and Sod Mimeticsmentioning

confidence: 99%

“…Recent insights into the mechanism of radiation-induced lung injury [5][6][7] have opened new opportunities for therapeutic intervention. A new therapeutic approach is targeted against the continuous production of reactive oxygen/reactive nitrogen species (ROS/RNS) in an ongoing process that perpetuates lung injury [5].…”

Section: Introductionmentioning

confidence: 99%

Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection

Gauter-Fleckenstein

Fleckenstein

Owzar

et al. 2008

Free Radical Biology and Medicine

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109

131

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Development of radiation (RT) induced lung injury is associated with chronic production of reactive oxygen and nitrogen species (ROS/RNS). MnTE-2-PyP 5+ is a catalytic Mn porphyrin (MnP) mimic of SOD, already shown to protect lungs from RT induced injury by scavenging ROS/RNS. The purpose of this study was to compare MnTE-2-PyP 5+ with the newly synthesized MnTnHex-2-PyP 5+ which is expected to be a more effective radioprotector due to its lipophilic properties. This study shows that Fischer rats which were irradiated to their right hemithorax (28 Gy) have less pulmonary injury as measured with breathing frequencies when treated with daily subcutaneous injections of MnTE-2-PyP 5+ (3 and 6 mg/kg) or MnTnHex-2-PyP 5+ (0.3 -0.6 -1.0 mg/kg) for 2 weeks after RT. However, at 16 weeks post RT, only MnTE-2-PyP 5+ at a dose of 6 mg/kg is able to ameliorate oxidative damage, block activation of HIF-1α and TGF-β and impair upregulation of CA-IX and VEGF. MnTnHex-2-PyP 5+ at a dose of 0.3 mg/kg is effective only in reducing RT-induced TGF-β and CA-IX expression. Significant loss in bodyweight was observed in animals receiving MnTnHex-2-PyP 5+ (0.3 and 0.6 mg/kg). MnTnHex-2-PyP 5+ has the ability to dissolve lipid membranes causing local irritations/necrosis at injection sites if given at doses of 1 mg/kg or higher. In conclusion, both compounds show ability to ameliorate lung damage as measured with breathing frequencies and histopathologic evaluation. However, MnTE-2-PyP 5+ at 6 mg/kg proved to be more effective in reducing expression of key molecular factors known to play an important role in radiation-induced lung injury.

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A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma

et al. 2022

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Background Childhood Hodgkin lymphoma survivors suffer from long‐term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%. Aims This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy. Methods and Results In this single‐center, 20‐year retrospective cohort study, we included patients who were <18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2 months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1–2 years after treatment completion, some children with these risk factors did not. Conclusion Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

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Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

Cited by 132 publications

References 39 publications

Effects of genistein following fractionated lung irradiation in mice

Effects of genistein following fractionated lung irradiation in mice

Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection

A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma

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