title: Formation of reactive oxygen and nitrogen species in the presence of pinosylvin - an analogue of resveratrol.
abstract: OBJECTIVE
  Formation of reactive oxygen species in neutrophils of rats with adjuvant arthritis and generation of nitric oxide in RAW 264.7 macrophages were analysed in the presence of pinosylvin.
  
  
  RESULTS
  The method of chemiluminescence was used for the detection of reactive oxygen species in blood of rats with adjuvant arthritis. Pinosylvin (50 mg/kg, daily, p.o.) and methotrexate (0.4 mg/kg, twice a week, p.o.) were applied separately or in a combination over a period of 28 days from the day of immunisation. Adjuvant arthritis was accompanied by a significantly increased number of neutrophils, by elevated concentration of oxidants in blood and by excessive responsiveness of neutrophils to stimulation with PMA. In rats treated with methotrexate, all these changes were significantly reduced and the inhibition became more pronounced when methotrexate was applied in the combination with pinosylvin; the monotherapy with pinosylvin did not induce any detectable changes in the parameters tested. Under in vitro conditions, pinosylvin inhibited formation of nitric oxide (NO) in macrophages, as demonstrated by the decreased concentration of nitrite - the end-product of NO metabolism (assessed by Griess' method), by the reduced expression of inducible NO synthase (detected by Western blot), and by the failure of pinosylvin to scavenge nitric oxide (measured amperometrically in cell-free system).
  
  
  CONCLUSIONS
  The observed ability of pinosylvin to decrease concentration of reactive oxygen and nitrogen species, along with its capacity to enhance the efficacy of methotrexate in arthritis treatment may shed more light into the pharmacological potential of this prospective natural substance.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. viera.jancinova@savba.sk
authors.forename: Viera
authors.initials: V
authors.lastname: Jancinova
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
authors.forename: Milan
authors.initials: M
authors.lastname: Ciz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ambrozova
authors.forename: Danica
authors.initials: D
authors.lastname: Mihalova
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
authors.forename: Tomas
authors.initials: T
authors.lastname: Perecko
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D000094162:Phytoalexins
chemical_list: D000975:Antioxidants; D018501:Antirheumatic Agents; D008727:Methotrexate; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D013267:Stilbenes; C049032:pinosylvin; D000094162:Phytoalexins