Radioprotective effect of pyrogallol nanocomposite on radiation-induced toxicity in spleen and bone marrow of BALB/c mice

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Background Radiotherapy is a first-line treatment for cancer that utilizes high-energy ionizing radiation to eliminate cancer cells. However, its therapeutic efficacy is often limited by their toxicity to healthy tissues. Therefore, the identification of effective radioprotective agents is necessary. To address this issue, our present study aimed to investigate the radioprotective potential of a pyrogallol nanocomposite (PyNC) in the irradiated spleen and bone marrow of BALB/c mice. Methods BALB/c mice were randomly assigned to four groups: control, radiation (10 Gy), radiation + PyNC (40 μg/kg body weight), and PyNC alone (40 μg/kg body weight). PyNC was administered to assess its protective effects against whole-body irradiation. The gene expression of apoptotic ( Bax, Bcl2, Caspase-3, Caspase-7, Caspase-9, p53, B220 ), inflammatory ( IL-1α, IL-6, IL-7, TNF-α ), and fibrotic ( TGF-β, Smad2, Smad3, Smad4 ) markers were evaluated using RT-PCR in irradiated spleen and bone marrow tissues. Additionally, the expression of apoptotic and inflammatory proteins were evaluated using Western blotting. The activities of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), were determined using antioxidant assays. Results PyNC treatment significantly attenuated radiation-induced molecular alterations in the spleen and bone marrow of mice. Compared with the irradiated group, PyNC significantly downregulated the expression of pro-apoptotic genes ( Bax, Caspase-3, Caspase-7, Caspase-9, p53 , and B220 ) ( p < 0.0001) and markedly upregulated the expression of the anti-apoptotic gene Bcl2 ( p < 0.0001), as confirmed by RT-PCR. PyNC also significantly attenuated the expression of pro-inflammatory genes ( IL-1α, IL-6, IL-7 , and TNF-α ) and fibrotic mediators ( TGF-β, Smad2, Smad3 , and Smad4 ) ( p < 0.0001). Furthermore, PyNC restored antioxidant defense by significantly increasing SOD ( p < 0.0001) and CAT (4 Gy: p = 0.0047; 8 Gy and 12 Gy: p < 0.0001) activities in irradiated bone marrow tissues. Conclusion PyNC demonstrated significant radioprotective activity by mitigating radiation-induced oxidative stress, inflammation, apoptosis, and fibrosis in the spleens and bone marrow of irradiated BALB/c mice. These findings suggest that PyNC is a promising candidate for reducing normal tissue toxicity during radiotherapy, although further mechanistic and translational studies are required.

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