Antioxidant effects of mycophenolate mofetil in a murine pleurisy model.
Generation of oxidative stress induced by reactive oxygen species (ROS) and nitrogen (RNS) is believed to be a primary factor in the etiology of various inflammatory diseases. Although, the process of generation of oxygen species is a physiological event, in the inflammatory process this event is increased and produces large amounts of reactive species that leads to lipid peroxidation and to cell death. Mycophenolate mofetil (MMF) is a drug effective in protecting against chronic allograft failure and recently was introduced as an alternative for the treatment of various inflammatory diseases such as glomerulopathies, systemic lupus erythematosus and systemic vasculitis. Based on studies of the anti-inflammatory effect of MMF the aim of this study was to evaluate the effects of MMF on the inhibition of leukocytes and exudation, as well as myeloperoxidase and some antioxidant enzyme activities using carrageenan-induced pleurisy in mice. Our results showed that MMF significantly decreased leukocyte influx (P<0.01), exudation (P<0.01), superoxide dismutase (P<0.05), catalase (P<0.05), glutathione peroxidase (P<0.01), glutathione S-transferase (P<0.01) activities, levels of lipid peroxidation (P<0.05), as well as myeloperoxidase activity (P<0.05) on both phases (4h and 48h) of the inflammatory response induced by carrageenan into the mice pleural cavity. In conclusion, the anti-inflammatory effect of MMF may be, at least in part, via inhibition of ROS and/or NRS overgeneration, and consequently, attenuating the related oxidative stress.
Dalmarco
Eduardo Monguilhott
EM
Department of Pharmaceutical Science, Health Sciences Center, University Regional of Blumenau, Itoupava Seca, Blumenau, SC 89000-030, Brazil.
Budni
Patrícia
P
Parisotto
Eduardo Benedetti
EB
Wilhelm Filho
Danilo
D
Fröde
Tânia Silvia
TS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use*; D002351:Carrageenan / Q000494:pharmacology; D002374:Catalase / Q000097:blood; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000097:blood; D005982:Glutathione Transferase / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D009504:Neutrophils / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D010996:Pleural Effusion / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D010998:Pleurisy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017392:Thiobarbituric Acid Reactive Substances; D003907:Dexamethasone; D002351:Carrageenan; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D009173:Mycophenolic Acid; D007213:Indomethacin