title: Attenuation of genotoxicity, oxidative stress, apoptosis and inflammation by rutin in benzo(a)pyrene exposed lungs of mice: plausible role of NF-κB, TNF-α and Bcl-2.
abstract: BACKGROUND
  Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice.
  
  
  METHODS
  Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation.
  
  
  RESULTS
  B(a)P enhanced lipid peroxidation, xanthine oxidase, H2O2 generation and lactate dehydrogenase (LDH) activity; depleted activities of anti-oxidant enzymes and glutathione content; induced DNA strand breaks and fragmentation; disrupted normal histopathological architecture and also showed abnormal expression of NF-κB, COX-2, IL-6, TNF-α and Bcl-2. Rutin pretreatment caused a significant reduction in lipid peroxidation and LDH activity; increased glutathione content; restored antioxidant enzyme activity; reduced DNA strand breaks and fragmentation; modulated the expression of inflammatory, and apoptotic markers and restored the histopathological structure.
  
  
  CONCLUSIONS
  The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity.
authors.forename: Ayaz
authors.initials: A
authors.lastname: Shahid
authors.forename: Rashid
authors.initials: R
authors.lastname: Ali
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.forename: Syed Kazim
authors.initials: SK
authors.lastname: Hasan
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.forename: Ferial
authors.initials: F
authors.lastname: Majed
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D011014:Pneumonia / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology; D012431:Rutin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D015850:Interleukin-6; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; D012431:Rutin; D004247:DNA; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase