Antagonistic effects of Zingerone, a phenolic alkanone against radiation-induced cytotoxicity, genotoxicity, apoptosis and oxidative stress in Chinese hamster lung fibroblast cells growing in vitro.
Zingerone (ZO), a dietary phenolic compound was investigated for its ability to protect against radiation-induced oxidative stress and DNA damage in Chinese hamster fibroblast cells (V79). Cells treated with optimal dose of ZO (25 μg/ml), 1 h prior radiation exposure resulted in a significant (P<0.01) elevation of cell survival and decreased the genotoxicity (micronuclei and comet assays). Further, pretreatment with ZO significantly reduced radiation-induced oxidative stress as indicated by decreased reactive oxygen species levels and inhibition of mitochondrial depolarisation. The experiments conducted to evaluate the intracellular antioxidant activity in ZO-pretreated cells demonstrated a significant (P<0.01) increase in the various antioxidants like glutathione, gluthione-S-transferase, superoxide dismutase, catalase and a significant (P<0.01) decrease in malondialdehyde levels versus irradiation alone. Further, ZO scavenged various free radicals generated in vitro (OH·, O(2)·, DPPH·, ABTS·(+) and NO·) in a dose-dependent manner. The anti-apoptotic effect of ZO pretreatment was by the inhibition of the activation of capase-3, by upregulating Bcl-2 and down-regulating Bax proteins. Our study demonstrates the antagonistic effect of ZO against radiation-induced cytotoxicity. Further, ZO rendered anti-genotoxic, anti-apoptotic and anti-lipid peroxidative potency, plausibly ascribable to its antioxidant/free radical scavenging ability and also by the suppression of radiation-induced oxidative stress.
Rao
B Nageshwar
BN
Division of Radiobiology and Toxicology, Manipal Life Sciences Centre, Manipal University, Manipal 576104, Karnataka, India.
Rao
B S Satish
BS
D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D010636:Phenols / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
D000473:Alkanes; D000975:Antioxidants; D010636:Phenols; C013738:zingerone; D006139:Guaiacol