Metformin prolongs survival rate in mice and causes increased excretion of cell-free DNA in the urine of X-irradiated rats

Abdullaev, S. A.; Minkabirova, G. M.; Karmanova, E. E.; Брусков, В. И.; Gaziev, A.I.

doi:10.1016/j.mrgentox.2018.05.006

Cited by 7 publications

(11 citation statements)

References 47 publications

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“…The obtained results indicated that at the doses of 4, 5 and 6 Gy, the X-ray did not cause any death of mice after 20 days post-irradiation; however, the dose of 7 Gy caused some deaths of mice after 7 days post-irradiation. This result was consistent with results reported in previous studies [24,25,26,27]. Based on this, we selected the dose of 6.0 Gy for further experiments.…”

Section: Resultssupporting

confidence: 92%

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Loc

Tri

et al. 2019

Materials

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Radiotherapy side-effects present serious problems in cancer treatment. Melanin, a natural polymer with low toxicity, is considered as a potential radio-protector; however, its application as an agent against irradiation during cancer treatment has still received little attention. In this study, nanomelanin particles were prepared, characterized and applied in protecting the spleens of tumor-bearing mice irradiated with X-rays. These nanoparticles had sizes varying in the range of 80–200 nm and contained several important functional groups such as carboxyl (-COO), carbonyl (-C=O) and hydroxyl (-OH) groups on the surfaces. Tumor-bearing mice were treated with nanomelanin at a concentration of 40 mg/kg before irradiating with a single dose of 6.0 Gray of X-ray at a high dose rate (1.0 Gray/min). Impressively, X-ray caused mild splenic fibrosis in 40% of nanomelanin-protected mice, whereas severe fibrosis was observed in 100% of mice treated with X-ray alone. Treatment with nanomelanin also partly rescued the volume and weight of mouse spleens from irradiation through promoting the transcription levels of splenic Interleukin-2 (IL-2) and Tumor Necrosis Factor alpha (TNF-α). More interestingly, splenic T cell and dendritic cell populations were 1.91 and 1.64-fold higher in nanomelanin-treated mice than those in mice which received X-ray alone. Consistently, the percentage of lymphocytes was also significantly greater in blood from nanomelanin-treated mice. In addition, nanomelanin might indirectly induce apoptosis in tumor tissues via activation of TNF-α, Bax, and Caspase-3 genes. In summary, our results demonstrate that nanomelanin protects spleens from X-ray irradiation and consequently enhances immunoactivity in tumor-bearing mice; therefore, we present nanomelanin as a potential protector against damage from radiotherapy in cancer treatment.

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Section: Resultssupporting

confidence: 92%

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Loc

Tri

et al. 2019

Materials

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“…5b). Thus, MF is effective when administered immediately post-irradiation, consistent with survival data gained in mice (Abdullaev et al 2018).…”

Section: Radiomitigatory Properties Of Metforminsupporting

confidence: 80%

“…The damage to mtDNA and mutations in mitochondrial genes encoding the subunits of respiratory enzymes reduce the production of ATP, which is necessary for repair processes, and entail further injuries to the mitochondria (Richter 1992). MF is considered precisely as a mitochondria-targeted radiomitigator (Abdullaev et al 2018), which inhibits the respiratory chain and prevents hyper-production of ROS.…”

Section: Discussionmentioning

confidence: 99%

“…Redox stress leads to genetic instability, an increase in the rate of mutations, loss of proteostasis, a decrease in life expectancy and to various diseases, including malignant tumors. There are few reports in the literature that MF is a potential versatile radiation modulator and radioprotector/radiomitigator (Miller et al 2014;Abdullaev et al 2018;Mortezaee et al 2019;Yahyapour et al 2019;Tajabadi et al 2020;Wang et al 2020). Thus, MF is a promising therapeutic agent capable of effectively ameliorating radiation toxicity.…”

Section: Introductionmentioning

confidence: 99%

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Metformin mitigates radiation toxicity exerting antioxidant and genoprotective properties

Karmanova

Chernikov

Popova

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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The antidiabetic drug metformin (MF) exhibits redox-modulating effects in various pathologies associated with oxidative stress and mitigates ionizing radiation-induced toxicity, but the underlying mechanisms remain to be elucidated. Thus, we studied some radiomitigatory effects of MF and explored the possible mechanisms behind them. Highly sensitive luminescence methods and non-competitive enzyme-linked immunosorbent assay (ELISA) were used in in vitro studies, and in vivo the damage to bone marrow cells and its repair were assessed by the micronucleus test. In a solution, MF at concentrations exceeding 0.1 µM effectively intercepts •OH upon X-ray-irradiation, but does not react directly with H 2 O 2 . MF accelerates the decomposition of H 2 O 2 catalyzed by copper ions. MF does not affect the radiation-induced formation of H 2 O 2 in the solution of bovine gamma-globulin (BGG), but has a modulating effect on the generation of H 2 O 2 in the solution of bovine serum albumin (BSA). MF at 0.05-1 mM decreases the radiation-induced formation of 8-oxoguanine in a DNA solution depending on the concentration of MF with a maximum at 0.25 mM. MF at doses of 3 mg/kg body weight (bw) and 30 mg/ kg bw administered to mice after irradiation, but not before irradiation, reduces the frequency of micronucleus formation in polychromatophilic erythrocytes of mouse red bone marrow. Our work has shown that the radiomitigatory properties of MF are mediated by antioxidant mechanisms of action, possibly including its ability to chelate polyvalent metal ions.

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“…However, the results of these studies are controversial. Some studies showed that metformin exhibited a radioprotective effect only when administered to mice after radiation exposure [ 7 ]. Therefore, the time at which metformin should be administered to generate a radioprotective effect still needs to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with metformin protects mice from whole-body irradiation

Guo

Yao

et al. 2021

Journal of Radiation Research

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Metformin, a first-line oral drug for type II diabetes mellitus, not only reduces blood glucose levels, but also has many other biological effects. Recent studies have been conducted to determine the protective effect of metformin in irradiation injuries. However, the results are controversial and mainly focus on the time of metformin administration. In this study, we aimed to investigate the protective effect of metformin in BALB/c mice exposed to 6 Gy or 8 Gy of a 60Co source of γ-rays for total body irradiation (TBI). Survival outcomes were assessed following exposure to 8 Gy or 6 Gy TBI, and hematopoietic damage and intestinal injury were assessed after exposure to 6 Gy TBI. Metformin prolonged the survival of mice exposed to 8 Gy TBI and improved the survival rate of mice exposed to 6 Gy TBI only when administered before exposure to irradiation. Moreover, pretreatment with metformin reduced the frequency of micronuclei (MN) in the bone marrow of mice exposed to 6 Gy TBI. Pretreatment of metformin also protected the intestinal morphology of mice, reduced inflammatory response and decreased the number of apoptotic cells in intestine. In conclusion, we demonstrated that pretreatment with metformin could alleviate irradiation injury.

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Metformin prolongs survival rate in mice and causes increased excretion of cell-free DNA in the urine of X-irradiated rats

Cited by 7 publications

References 47 publications

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Metformin mitigates radiation toxicity exerting antioxidant and genoprotective properties

Pretreatment with metformin protects mice from whole-body irradiation

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