Metformin Ameliorates 2.856 GHz Microwave-Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis

Abstract

Metformin Ameliorates 2.856 GHz Microwave-Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis Men J, Zhang L, Peng R, Li Y, Li M, Wang H, Zhao L, Zhang J, Wang H, Xu X, Dong J, Wang J, Yao B, Guo J. Metformin Ameliorates 2.856 GHz Microwave- Radiation-Induced Reproductive Impairments in Male Rats via Inhibition of Oxidative Stress and Apoptosis. Int J Mol Sci. 2023 Jul 31;24(15):12250. doi: 10.3390/ijms241512250. Abstract The reproductive system has been increasingly implicated as a sensitive target of microwave radiation. Oxidative stress plays a critical role in microwave radiation -induced reproductive damage, though precise mechanisms are obscure. Metformin, a widely used antidiabetic drug, has emerged as an efficient antioxidant against a variety of oxidative injuries. In the present study, we hypothesized that metformin can function as an antioxidant and protect the reproductive system from microwave radiation. To test this hypothesis, rats were exposed to 2.856 GHz microwave radiation for 6 weeks to simulate real-life exposure to high-frequency microwave radiation. Our results showed that exposure to 2.856 GHz microwave radiation elicited serum hormone disorder, decreased sperm motility, and depleted sperm energy, and it induced abnormalities of testicular structure as well as mitochondrial impairment. Metformin was found to effectively protect the reproductive system against structural and functional impairments caused by microwave radiation. In particular, metformin can ameliorate microwave-radiation-induced oxidative injury and mitigate apoptosis in the testis, as determined by glutathione/-oxidized glutathione (GSH/GSSG), lipid peroxidation, and protein expression of heme oxygenase-1 (HO-1). These findings demonstrated that exposure to 2.856 GHz microwave radiation induces obvious structural and functional impairments of the male reproductive system, and suggested that metformin can function as a promising antioxidant to inhibit microwave-radiation-induced harmful effects by inhibiting oxidative stress and apoptosis. Excerpts ... the SAR value of 30 mW/cm2 microwave radiation to testicular tissue in this experiment was 34.2 W/kg, and the whole-body average SAR value for rats was 10.17 W/kg.... Metformin not only acts as a free radical scavenger to reduce free radical production, but also reduces radiation- induced apoptosis [65]. In the reproductive system, metformin has been shown to reduce germ-cell-specific oxidative-stress-induced apoptosis that improves sperm quality after testicular damage [31]. Moreover, many studies have shown that microwave radiation induces free radical formation and excessive ROS accumulation in testicular tissue, causing activation of apoptosis [24,66,67]. In the present study, we used Bax/Bcl-2 and cleaved caspase-3 to detect apoptosis in testicular tissues. The results revealed that the Bax/Bcl-2 ratio and the expression of the cleaved caspase-3 were increased by 2.856 GHz microwave radiation exposure, and the increases were inhibited by metformin, indicating an important role for metformin against microwave-radiation- induced apoptosis. In conclusion, our results demonstrated that exposure to 2.856 GHz microwave radiation for 6 weeks caused obvious structural and functional impairments in the reproductive system and that rats still had not fully recovered from reproductive damage 28 days after radiation exposure, but that metformin protected against reproductive impairments, at least in part by inhibiting oxidative stress and apoptosis. The mechanisms and sensitive targets need to be further elucidated by sequencing, knockdown, or overexpression experiments. Open access paper: mdpi.com

AI evidence extraction

Main findings

Exposure to 2.856 GHz microwave radiation for 6 weeks was associated with serum hormone disorder, decreased sperm motility, depleted sperm energy, abnormal testicular structure, and mitochondrial impairment. Metformin was reported to protect against these structural and functional impairments and to reduce oxidative injury and apoptosis markers in testicular tissue; the abstract also states rats had not fully recovered 28 days after exposure.

Outcomes measured

• Male reproductive system structural impairments (testicular structure abnormalities, mitochondrial impairment)
• Serum hormone disorder
• Sperm motility
• Sperm energy depletion
• Oxidative stress markers (GSH/GSSG, lipid peroxidation, HO-1)
• Apoptosis markers in testis (Bax/Bcl-2 ratio, cleaved caspase-3)
• Recovery status 28 days after exposure

Limitations

• Sample size not reported in provided text
• Exposure source/context described as simulating real-life exposure, but specific source details not provided
• Findings are from an animal model (rats), limiting direct generalization to humans

{
    "study_type": "animal",
    "exposure": {
        "band": "microwave",
        "source": null,
        "frequency_mhz": 2856,
        "sar_wkg": 34.2000000000000028421709430404007434844970703125,
        "duration": "6 weeks"
    },
    "population": "Male rats",
    "sample_size": null,
    "outcomes": [
        "Male reproductive system structural impairments (testicular structure abnormalities, mitochondrial impairment)",
        "Serum hormone disorder",
        "Sperm motility",
        "Sperm energy depletion",
        "Oxidative stress markers (GSH/GSSG, lipid peroxidation, HO-1)",
        "Apoptosis markers in testis (Bax/Bcl-2 ratio, cleaved caspase-3)",
        "Recovery status 28 days after exposure"
    ],
    "main_findings": "Exposure to 2.856 GHz microwave radiation for 6 weeks was associated with serum hormone disorder, decreased sperm motility, depleted sperm energy, abnormal testicular structure, and mitochondrial impairment. Metformin was reported to protect against these structural and functional impairments and to reduce oxidative injury and apoptosis markers in testicular tissue; the abstract also states rats had not fully recovered 28 days after exposure.",
    "effect_direction": "mixed",
    "limitations": [
        "Sample size not reported in provided text",
        "Exposure source/context described as simulating real-life exposure, but specific source details not provided",
        "Findings are from an animal model (rats), limiting direct generalization to humans"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "microwave radiation",
        "2.856 GHz",
        "male rats",
        "reproductive toxicity",
        "testis",
        "sperm motility",
        "oxidative stress",
        "apoptosis",
        "metformin",
        "SAR"
    ],
    "suggested_hubs": []
}

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