Modification of radiation damage to mitochondrial system in vivo by Podophyllum hexandrum: mechanistic aspects.
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 y-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.
Gupta
Damodar
D
Radiation Biology Division, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Arora
Rajesh
R
Garg
Amar Prakash
AP
Bala
Madhu
M
Goel
Harish Chandra
HC
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D042967:Electron Transport Complex I / Q000378:metabolism; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000528:radiation effects; D008297:Male; D008564:Membrane Potentials / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D011035:Podophyllum / Q000737:chemistry*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014916:Whole-Body Irradiation
D010936:Plant Extracts; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013384:Succinate Cytochrome c Oxidoreductase; D042967:Electron Transport Complex I; D005978:Glutathione