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Modification of radiation damage to mitochondrial system in vivo by Podophyllum hexandrum: Mechanistic aspects

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The present study was undertaken to investigate whether RP-1 treatment protected mitochondrial system against radiation damage and also to unravel the mechanism associated with this process. Radioprotection of mitochondrial system by Podophyllum hexandrum (RP-1) was investigated to understand its mechanism of action. Levels of superoxide anion (O2−), reduced or oxidized glutathione (GSH or GSSG), thiobarbituric acid reactive substance (TBARS), protein carbonyl (PC), ATP, NADH-ubiquinone oxidoreductase (complex-I), NADH-cytochrome c oxidoreductase (complex I/II), succinate-cytochrome c oxidoreductase (complex II/III) and mitochondrial membrane potential (MMP) were studied in mitochondria isolated from liver of mice belonging to various treatment groups. Whole body γ-irradiation (10 Gy) significantly (p < 0.01) increased the formation of O2−, PC, and TBARS, upto 24 h as compared to untreated control. RP-1 treatment (200 mg/kg b.w.) to mice 2 h before irradiation reduced the radiation-induced O2− generation within 4 h and formation of TBARS and PC upto 24 h significantly (p < 0.01). Singularly irradiation or RP-1 treatment significantly (p < 0.01) increased the levels of glutathione within an hour, as compared to untreated control. Pre-irradiation administration of RP-1 enhanced levels of GSH induced increase in complex I (upto 16 h), complex I/III (4 h) complex II/III activity (upto 24 h;p < 0.01) and inhibited the radiation-induced decrease in MMP significantly (24 h;p < 0.01). The present study indicates that RP-1 itself modulates several mitichondrial perameters due to its influence on the biochemical milieu within and outside the cells. However, RP-1 treatment before irradiation modulates radiation induced perturbations such as the increase in electron transport chain enzyme activity, formation of O2−, TBARS and PC to offer radioprotection (Mol Cell Biochem 266: 65–77, 2004)

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Authors and Affiliations

  1. Radiation Biology Division, Institute of Nuclear Medicine and Allied Sciences, Delhi, India

    Damodar Gupta, Rajesh Arora & Madhu Bala

  2. Department of Microbiology, Chaudhary Charan Singh University, Meerut, India

    Amar Prakash Garg & Harish Chandra Goel

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  1. Damodar Gupta
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  2. Rajesh Arora
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  4. Madhu Bala
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  5. Harish Chandra Goel
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Gupta, D., Arora, R., Garg, A.P. et al. Modification of radiation damage to mitochondrial system in vivo by Podophyllum hexandrum: Mechanistic aspects. Mol Cell Biochem 266, 65–77 (2004). https://doi.org/10.1023/B:MCBI.0000049139.05337.40

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