Abstract: FR-PO1001
Magnesium Protects Against CKD Progression by Reducing DNA Damage
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Matsubara, Makoto, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Sasaki, Kensuke, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Ishiuchi, Naoki, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Takahashi, Akira, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Osaki, Yosuke, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Maeoka, Yujiro, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
- Masaki, Takao, Hiroshima Daigaku Daigakuin Ikei Kagaku Kenkyuka, Hiroshima, Hiroshima, Japan
Background
DNA damage accelerates the the progression of chronic kidney disease (CKD) and kidney aging. Emerging evidence suggests that magnesium (Mg) has the ability to suppress DNA damage by promoting chromatin aggregation. In this study, we aimed to investigate the potential of Mg administration in reducing DNA damage and mitigating the progression of CKD.
Methods
Male C57BL/6 mice (8 weeks old) were treated with a dosage of 600 mg/kg of Mg or deionized distilled water (DDW) and were subjected to renal irradiation with 8 Gy of radiation. As another model, male C57BL/6 mice (8 weeks old) underwent unilateral ischemia/reperfusion (I/R) injury with renal pedicle clamping for 35 minutes. These mice received Mg or DDW every 12 hours after I/R. Then, mice were sacrificed one- or three-week after I/R. In vitro experiments were also conducted using rat renal tubular (NRK52E) and rat kidney fibroblast (NRK49F) cells, which were irradiated with 1 Gy of radiation at different Mg concentrations (0.8mM, 3.2mM, 6.4mM) in the medium.
Results
Western blotting analysis revealed that the effects of radiation injury were confirmed by an increase of γH2AX, a marker of DNA double-strand breaks. Mice were treated with 600 mg/kg of Mg and subjected to renal irradiation with 8 Gy of radiation. Remarkably, the Mg-treated group exhibited reduced levels of γH2AX in the kidneys compared to the non-treated group. Furthermore, NRK52E and NRK49F cells irradiated with 1 Gy of radiation showed a reduction in γH2AX levels as the Mg concentration in the medium increased (0.8 mM, 3.2 mM, 6.4 mM). In the one-week I/R model, Western blotting analysis revealed that Mg administration resulted in a reduction of DNA damage markers (γH2AX and rad51), markers of aging (p16 and p21) and the inflammation marker (cGAS-Sting). Immunostaining demonstrated that Mg administration resulted in a reduction of markers of aging (p16 and p21) and the inflammation marker (F4/80). Furthermore, real-time PCR analysis indicated that Mg administration led to a decrease in markers of inflammation (IL-6 and IL-1β). In the three-week I/R model, Western blotting and immunostaining revealed that fibrotic markers (αSMA and collagen I) were also reduced in the Mg-treated group.
Conclusion
Administration of Magnesium reduces DNA damage and mitigates renal I/R injury, including aging, inflammation and fibrosis.