title: The influence of lentinan on the capacity of repair of DNA damage and apoptosis induced by paclitaxel in mouse bone marrow cells.
abstract: The ability of the flavonoid lentinan (LAN) to enhance the repair of paclitaxel (PAC)-induced DNA damage and apoptosis in mouse bone marrow cells was investigated. Moreover, the possible mechanism underlying this modulation was determined. LAN was neither genotoxic nor apoptogenic at doses equivalent to 1 or 2 mg/kg/day. Pretreatment of mice with LAN significantly enhances the repair of PAC-induced DNA damage and bone marrow suppression in a dose dependent manner. Moreover, LAN affords significant protection against PAC-induced apoptosis. A significant increase of reactive oxygen species and a decrease in reduced glutathione levels were observed after PAC treatment and prior administration of LAN before PAC challenge ameliorated these oxidative stress markers. Conclusively, our study provides, for the first time, that LAN enhances the repair of PAC-induced DNA damage and apoptosis that resides, at least in part, on its ability to modulate the cellular antioxidant levels and consequently protect bone marrow cells from PAC genotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. attiasm@ksu.edu.sa
authors.forename: Sabry M
authors.initials: SM
authors.lastname: Attia
authors.forename: Gamaleldin I
authors.initials: GI
authors.lastname: Harisa
authors.forename: Adel R
authors.initials: AR
authors.lastname: Abd-Allah
authors.forename: Sheikh Fayaz
authors.initials: SF
authors.lastname: Ahmad
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Bakheet
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D007912:Lentinan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000009:adverse effects* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D007912:Lentinan; D017239:Paclitaxel
keywords: Apoptosis; Bone Marrow Suppression; DNA Damage and Repair; Lentinan; Oxidative Stress; Secondary Malignancies