Melatonin's protective effect on the salivary gland against ionized radiation damage in rats

Karaer, Işıl Çakmak; Şimşek, Gökçe; Yıldız, Azibe; Vardı, Nigar; Polat, Alaadin; Tanbek, Kevser; Gurocak, Simay; Parlakpınar, Hakan

doi:10.1111/jop.12386

Cited by 31 publications

(7 citation statements)

References 34 publications

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“…Similar results were obtained with Zhang et al, who found that the IP injection of melatonin markedly reduced the pulmonary injury and decreased the infiltration of macrophages and neutrophils into the lung [23]. As reported by others [24], melatonin protects the irradiated cells by supporting endogenous antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, while suppressing prooxidant enzymes. Accordingly, the radioprotection mechanism can be attributed to the scavenging of free radicals and attenuation of lipid membrane peroxidation and neutrophil-induced infiltration [25].…”

Section: Discussionsupporting

confidence: 87%

Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Melatonin is a well-known anti-inflammatory and antioxidant molecule, which plays a crucial role in various physiological functions. In this study, mice received a single dose of 15 Gy radiation delivered to the lungs and daily intraperitoneal administration of melatonin. After 7 days, mice were processed to harvest either bronchoalveolar lavage fluid for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that melatonin markedly alleviated the oxidative stress and injury, especially suppressing the infiltration of macrophages (CD11b+CD11c−) and neutrophils (CD11b+Ly6G+) to the irradiated lungs. Moreover, in the irradiated RAW 264.7 cells, melatonin blocked the NLRP3 inflammasome activation accompanied with the inhibition of the IL-1β release and caspase-1 activity. However, melatonin restored the downregulated miR-30e levels. Quantitative PCR analysis of miR-30e and NLRP3 indicated the negative correlation between them. Notably, immunofluorescence staining showed that overexpression of miR-30e dramatically diminished the increased NLRP3 expression. Luciferase reporter assay confirmed that NLRP3 was a target gene of miR-30e. Western blotting revealed that transfection with miR-30e mimics markedly reduced the expressions of NLRP3 and cleaved caspase-1, whereas this phenomenon was reversed by the miR-30e inhibitor. Consistent with this, the beneficial effect of melatonin under irradiated exposure was blunted in cells transfected with anti-miR-30e. Collectively, our results demonstrate that the NLRP3 inflammasome contributed to the pathogenesis of radiation-induced lung injury. Meanwhile, melatonin exerted its protective effect through negatively regulating the NLRP3 inflammasome in macrophages. The melatonin-mediated miR-30e/NLRP3 signaling may provide novel therapeutic targets for radiation-induced injury.

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Section: Discussionsupporting

confidence: 87%

Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…The findings of other studies have shown that some substances that are demonstrated to be effective against the adverse effects of radiotherapy also lead to reductions in oxidative stress parameters. 4,14 In comparison to the control group, the TOS and OSI values measured in our study in both the submandibular gland tissue and the blood were found to be significantly higher only in the group given radiotherapy without additional treatment. This finding in the radiotherapy model we established shows that radiotherapy also leads to increases in oxidative stress in addition to histopathological degeneration.…”

Section: Discussioncontrasting

confidence: 48%

Protective Effect of Whortleberry Extract on Salivary Gland Damage Induced by Neck Irradiation in Rats

Özgür

Terzi

Özdemir

et al. 2019

Ear, Nose & Throat Journal

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Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased ( P < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.

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“…To enhance cellular antioxidant capacity, somatic strategies can confer purely localized benefits, such as those presented by heat shock protein 25 and melatonin on the salivary gland, or by SOD3 on the lungs ( 82 , 91 , 92 ). The local benefits of upregulating production of some enzymes are summarized in Figure 1 .…”

Section: Discussion: Radioprotective Transgenesmentioning

confidence: 99%

Contemporary biomedical engineering perspective on volitional evolution for human radiotolerance enhancement beyond low-earth orbit

Borg

Baker

2021

Synthetic Biology

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A primary objective of the National Aeronautics and Space Administration (NASA) is expansion of humankind’s presence outside low-Earth orbit, culminating in permanent interplanetary travel and habitation. Having no inherent means of physiological detection or protection against ionizing radiation, humans incur capricious risk when journeying beyond low-Earth orbit for long periods. NASA has made large investments to analyze pathologies from space radiation exposure, emphasizing the importance of characterizing radiation’s physiological effects. Because natural evolution would require many generations to confer resistance against space radiation, immediately pragmatic approaches should be considered. Volitional evolution, defined as humans steering their own heredity, may inevitably retrofit the genome to mitigate resultant pathologies from space radiation exposure. Recently, uniquely radioprotective genes have been identified, conferring local or systemic radiotolerance when overexpressed in vitro and in vivo. Aiding in this process, the CRISPR/Cas9 technique is an inexpensive and reproducible instrument capable of making limited additions and deletions to the genome. Although cohorts can be identified and engineered to protect against radiation, alternative and supplemental strategies should be seriously considered. Advanced propulsion and mild synthetic torpor are perhaps the most likely to be integrated. Interfacing artificial intelligence with genetic engineering using predefined boundary conditions may enable the computational modeling of otherwise overly complex biological networks. The ethical context and boundaries of introducing genetically pioneered humans are considered.

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Melatonin's protective effect on the salivary gland against ionized radiation damage in rats

Abstract: Melatonin may have a significant protective effect on salivary gland damage secondary to ionizing radiation.

Cited by 31 publications

References 34 publications

Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

Melatonin Alleviates Radiation-Induced Lung Injury via Regulation of miR-30e/NLRP3 Axis

Protective Effect of Whortleberry Extract on Salivary Gland Damage Induced by Neck Irradiation in Rats

Contemporary biomedical engineering perspective on volitional evolution for human radiotolerance enhancement beyond low-earth orbit

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