title: Wogonin attenuates etoposide-induced oxidative DNA damage and apoptosis via suppression of oxidative DNA stress and modulation of OGG1 expression.
abstract: Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The current study has been initiated to determine whether the flavonoid wogonin can attenuate etoposide-induced oxidative DNA damage and apoptosis in mouse bone marrow cells. We found that oral administration of wogonin before etoposide injection significantly attenuates etoposide-induced oxidative DNA damage and apoptosis in a dose dependent manner. Etoposide induced a significant down-regulation of mRNA expression of the OGG1 repair gene and marked biochemical alterations characteristic of oxidative DNA stress, including increased 8-OHdG, enhanced lipid peroxidation and reduction in reduced glutathione. Prior administration of wogonin ahead of etoposide challenge restored these altered parameters. Importantly, wogonin had no antagonizing effect on etoposide-induce topoisomerase-II inhibition. Conclusively, our study indicates that wogonin has a protective role in the abatement of etoposide-induced oxidative DNA damage and apoptosis in the bone marrow cells of mice via suppression of oxidative DNA stress and enhancing DNA repair through modulation of OGG1 repair gene expression. Therefore, wogonin can be a promising chemoprotective agent and might be useful to avert secondary leukemia and other drug-related cancers in cured cancer patients and medical personnel exposing to the potent carcinogen etoposide.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. attiasm@ksu.edu.sa
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmad
authors.forename: Gamaleldin I
authors.initials: GI
authors.lastname: Harisa
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Mansour
authors.forename: El Sayed M
authors.initials: el SM
authors.lastname: El Sayed
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000009:adverse effects / Q000037:antagonists & inhibitors; D044950:Flavanones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007938:Leukemia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D059005:Topoisomerase II Inhibitors / Q000009:adverse effects / Q000737:chemistry
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D044950:Flavanones; D012333:RNA, Messenger; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; C085514:wogonin
keywords: Apoptosis; DNA damage/repair; Oxidative DNA stress; Secondary tumors