Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model

Oscarsson, Nicklas; Ny, Lars; Mölne, Johan; Lind, Folke; Ricksten, Sven‐Erik; Seeman-Lodding, H.; Giglio, Daniel

doi:10.1016/j.freeradbiomed.2016.12.036

Cited by 37 publications

(19 citation statements)

References 26 publications

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“…113 As previously described, irradiation leads to increased oxidative stress in the tissue, demonstrated by elevated levels of 8-OHdG. 114 Downstream effects include elevation of TGF-β, IL-1, TNF, and ICAM-1, all related to the development of fibrosis, which restricts the function of the urinary bladder. 115 The regenerative process is impaired by the chronic inflammation, senescence, and malfunction of normal cells previously injured by irradiation.…”

Section: Radiation-induced Injuries In the Urinary Bladdermentioning

confidence: 93%

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

Oscarsson

Müller

Rosén

et al. 2019

The Lancet Oncology

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Introduction Cancer is affecting a growing number of persons. Still, the treatment and survival of cancer is improving. Radiation therapy is used in the treatment of cancer. Late radiation-induced injuries afflict 5-15% of irradiated patients. The urinary bladder and bowel may be affected after irradiation of cancer in the pelvic region. Symptoms can be severe, with impaired health related quality of life (HRQoL). Hyperbaric oxygen therapy (HBOT) involves breathing oxygen at high ambient pressure. HBOT can reverse radiation-induced injuries, alleviate patient-perceived symptoms, and improve HRQoL. We aimed to clarify the effects of HBOT on late radiation-induced injuries in the urinary bladder and bowel, and to clarify some of the underlying mechanisms through which HBOT exerts its effects. Methods A prospective cohort study assessed effects of HBOT on patient-perceived symptoms (Paper I). A rat study assessed reversal of radiation-induced stress with HBOT (Paper II). A methodological experiment assessed reversal of HBOT on cellular death induced by radiation (Paper III). A multi-center, randomized, controlled trial assessed patient-perceived symptoms, HRQoL, and objective clinical outcomes (Paper IV). Result HBOT can alleviate patient-perceived symptoms, reduce objective findings, and improve HRQoL in patients affected by late radiation-induced injuries (Paper I, IV). Oxidative stress and downstream effects, induced by the irradiation, can be reversed by HBOT (Paper II). Paper III outlines a method for studies on urothelial cells exposed to radiation and HBOT. Conclusion HBOT can reduce radiation-induced oxidative stress and inflammatory response. HBOT can reverse injuries induced by radiation therapy to the pelvic region, alleviate patient-perceived symptoms and lead to improved HRQoL.

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Section: Radiation-induced Injuries In the Urinary Bladdermentioning

confidence: 93%

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

Oscarsson

Müller

Rosén

et al. 2019

The Lancet Oncology

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“…In addition to changes in neuronal signaling, structural changes may also contribute to bladder disturbances (e.g., the amount of collagen is increased in the bladder wall after irradiation) (Soler et al, 2011). In a rat model for radiation cystitis, we showed that bladder irradiation induces long-lasting changes in oxidative stress and cytokine levels in the urinary bladder (Giglio et al, 2016;Oscarsson et al, 2017).…”

Section: Introductionmentioning

confidence: 84%

Changes in the Neuronal Control of the Urinary Bladder in a Model of Radiation Cystitis

Giglio

Podmolíková

Tobin

2018

J Pharmacol Exp Ther

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Currently, we have assessed the neuronal control of the urinary bladder in radiation cystitis and whether interstitial cells contribute to the condition. Fourteen days after bladder irradiation (20 Gy), rats were sedated and the urinary bladder was cut into two sagittal halves where electrical field stimulation (EFS; 5-20 Hz) was applied on the pelvic nerve afferents or stretch (80 mN) on one-half of the bladder, while contractions were registered on the contralateral half of the bladder in the absence and presence of increasing doses of imatinib (1-10 mg/kg; inhibitor of c-kit-positive interstitial cells), atropine (1 mg/kg; to block muscarinic M receptors), or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (2 mg/kg; P2 purinoceptor antagonist). Urinary bladders were also excised for organ bath experiments, Western blot, quantitative polymerase chain reaction, and immunohistochemistry. In vivo, EFS contractions were enhanced after irradiation, and imatinib (1-10 mg/mg) inhibited contractions by EFS and stretched dose-dependently in controls but not in irradiated bladders. In the irradiated bladder in vitro, atropine resistance was increased and imatinib (100 M) inhibited contractions by EFS and agonists (ATP, methacholine) in irradiated bladders and controls. The urinary bladder expressions of P2 purinoceptors, muscarinic M receptor, choline acetyltransferase, c-kit, and the agonist of c-kit, stem cell factor, were not changed by irradiation. In conclusion, bladder irradiation affects several levels of neuronal control of the urinary bladder. Interstitial cells may contribute to some of the symptoms associated with radiation cystitis.

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“…Activation of certain immunological pathways may lead to later development of fibrosis as has been demonstrated for radiation-induced dermal fibrosis, colonic fibrosis and pulmonary fibrosis [4, 13, 14]. In an animal model for radiation cystitis, we observed that radiation may suppress TLR4 and immunoregulatory pathways and affect the antioxidative system of the urinary bladder [6, 15]. Therefore, we presently assessed in an animal model how the innate immune system and antioxidative system of the cervix respond to the exposure of high-dose ionising radiation in the early phase following cervical irradiation.…”

Section: Introductionmentioning

confidence: 94%

Radiation induces changes in toll-like receptors of the uterine cervix of the rat

et al. 2019

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Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1–14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2–9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2–9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.

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Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model

Cited by 37 publications

References 26 publications

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

Changes in the Neuronal Control of the Urinary Bladder in a Model of Radiation Cystitis

Radiation induces changes in toll-like receptors of the uterine cervix of the rat

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