Ameliorating effect of CpG-ODN (oligodeoxynucleotide) against radiation-induced lung injury in mice

Park, Kawngwoo; Dhupal, Madhusmita; Kim, Cheol-Su; Jung, Soon-Hee; Choi, Deahan; Qi, Xufeng; Kim, Soo‐Ki; Lee, Jong Yong

doi:10.1007/s00411-020-00871-w

Cited by 4 publications

(7 citation statements)

References 28 publications

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“…Cytosine–phosphate–guanine oligodeoxynucleotides (CpG-ODNs) are artificial unmethylated CpG motifs originally discovered in bacterial DNA [ 6 ]. As previously reported, CpG-ODN could confer ameliorating effect against radiation-induced lung injury in a mouse model [ 7 ]. CpG-ODN also upregulated G-CSF and IL-6 to improve irradiation-induced injuries [ 8 ].…”

Section: Introductionmentioning

confidence: 52%

“…Results of the study revealed that CpG-ODNs attenuated RKI by inhibiting DNA damage and oxidative stress levels. CpG-ODN played an alleviatory role in radiation-induced lung injury in a mouse model [ 7 ]. Several studies have suggested CpG-ODNs as an important inhibitor for radiation-induced pulmonary fibrosis [ 45 , 46 ] and bone marrow hemopoiesis injury [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that KSK CpG-ODN (K-CpG) effectively protects mice from radiation-induced lung injury by modulating innate immune responses [ 7 ]. Furthermore, research has indicated that all three types of ODNs can protect mice from radiation-induced damage, with B-grade ODNs demonstrating the most effective characteristics in radioprotection, possibly achieved through upregulating the expression of G-CSF and IL-6 [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the available literature [ 7 , 18 ], we used two types of CpG-ODNs for our study, CpG-ODN2216 and CpG-ODN2006 [ 19 ]. All CpG-ODNs were synthesized and purified by Sangon (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

“…Each mouse was intraperitoneally injected with 50 μg of CpG-ODNs or saline solution, five times per week, followed by every fourth session. The mice were exposed to X-ray irradiation, five times per week, for a total of 4 weeks [ 7 , 8 ].…”

Section: Methodsmentioning

confidence: 99%

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Cytosine–phosphate–guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis

Zhang,

et al. 2023

J Transl Med

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Background Radiotherapy can cause kidney injury in patients with cervical cancer. This study aims to investigate the possible molecular mechanisms by which CpG-ODNs (Cytosine phosphate guanine-oligodeoxynucleotides) regulate the PARP1 (poly (ADP-ribose) polymerase 1)/XRCC1 (X-ray repair cross-complementing 1) signaling axis and its impact on radiation kidney injury (RKI) in cervical cancer radiotherapy. Methods The GSE90627 dataset related to cervical cancer RKI was obtained from the Gene Expression Omnibus (GEO) database. Bioinformatics databases and R software packages were used to analyze the target genes regulated by CpG-ODNs. A mouse model of RKI was established by subjecting C57BL/6JNifdc mice to X-ray irradiation. Serum blood urea nitrogen (BUN) and creatinine levels were measured using an automated biochemical analyzer. Renal tissue morphology was observed through HE staining, while TUNEL staining was performed to detect apoptosis in renal tubular cells. ELISA was conducted to measure levels of oxidative stress-related factors in mouse serum and cell supernatant. An in vitro cell model of RKI was established using X-ray irradiation on HK-2 cells for mechanism validation. RT-qPCR was performed to determine the relative expression of PARP1 mRNA. Cell proliferation activity was assessed using the CCK-8 assay, and Caspase 3 activity was measured in HK-2 cells. Immunofluorescence was used to determine γH2AX expression. Results Bioinformatics analysis revealed that the downstream targets regulated by CpG-ODNs in cervical cancer RKI were primarily PARP1 and XRCC1. CpG-ODNs may alleviate RKI by inhibiting DNA damage and oxidative stress levels. This resulted in significantly decreased levels of BUN and creatinine in RKI mice, as well as reduced renal tubular and glomerular damage, lower apoptosis rate, decreased DNA damage index (8-OHdG), and increased levels of antioxidant factors associated with oxidative stress (SOD, CAT, GSH, GPx). Among the CpG-ODNs, CpG-ODN2006 had a more pronounced effect. CpG-ODNs mediated the inhibition of PARP1, thereby suppressing DNA damage and oxidative stress response in vitro in HK-2 cells. Additionally, PARP1 promoted the formation of the PARP1 and XRCC1 complex by recruiting XRCC1, which in turn facilitated DNA damage and oxidative stress response in renal tubular cells. Overexpression of either PARP1 or XRCC1 reversed the inhibitory effects of CpG-ODN2006 on DNA damage and oxidative stress in the HK-2 cell model and RKI mouse model. Conclusion CpG-ODNs may mitigate cervical cancer RKI by blocking the activation of the PARP1/XRCC1 signaling axis, inhibiting DNA damage and oxidative stress response in renal tubule epithelial cells.

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Section: Introductionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cytosine–phosphate–guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis

Zhang,

et al. 2023

J Transl Med

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Radiation sensitivity of biological systems, its modification by chemical modifiers and its quantitative evaluation

Múčka,

Čuba

2024

J Radioanal Nucl Chem

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Large number of sensitizers and protectors of cells, tissues, organs and organisms are being discussed in this review. Attention is paid to metals, nanoparticles or organic compounds as modifiers. They can modify the radiation sensitivity by 20–60%. In most cases, sensitization is caused by an increase in DNA damage or a decrease in the repair of radiation damage. The protection can be caused in many cases by repair of damaged DNA molecules, proteins or enzymes, or by reducing the ROS concentration. The most current research tasks in this area are formulated. A new quantitative and reproducible method of evaluating modifiers is discussed.

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Cytokine, chemokine alterations and immune cell infiltration in Radiation-induced lung injury: Implications for prevention and management

Guo,

Yu,

Zhang

et al. 2024

International Immunopharmacology

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Ameliorating effect of CpG-ODN (oligodeoxynucleotide) against radiation-induced lung injury in mice

Cited by 4 publications

References 28 publications

Cytosine–phosphate–guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis

Cytosine–phosphate–guanine oligodeoxynucleotides alleviate radiation-induced kidney injury in cervical cancer by inhibiting DNA damage and oxidative stress through blockade of PARP1/XRCC1 axis

Radiation sensitivity of biological systems, its modification by chemical modifiers and its quantitative evaluation

Cytokine, chemokine alterations and immune cell infiltration in Radiation-induced lung injury: Implications for prevention and management

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