title: Carnosine inhibits degradation of hyaluronan induced by free radical processes in vitro and improves the redox imbalance in adjuvant arthritis in vivo.
abstract: OBJECTIVE
  New ways of supplementary or combinatory therapy of rheumatoid arthritis (RA) are of great importance. The aim is to find an additive to classical RA therapy with natural molecules without side effects possessing anti-inflammatory and anti-oxidative properties. In this study we investigated the anti-oxidative and anti-inflammatory properties of the endogenous natural compound carnosine (CARN) in vitro and in vivo. Moreover, we tested also the inhibitory properties of the drug methotrexate (MTX) on dynamic viscosity of hyaluronan (HA) solutions in the same manner.
  
  
  METHODS
  For in vitro testing of the inhibitory properties of CARN against degradation of HA solutions, we used the model of degradation of hyaluronan (HA) induced by free radicals. Both substances, CARN and MTX, were compared to glutathione (GSH). Rotational viscometry was used in evaluation of protective properties of compounds studied. The ability of CARN to restore the redox imbalance occurring in adjuvant arthritis (AA) of rats was also tested. We monitored the effect of CARN on hind paw volume (HPV) and on the levels of protein carbonyls, and thiobarbituric acid reacting substances (TBARS) in AA.
  
  
  RESULTS
  In the reaction system with the prevalence of •OH and/or peroxy-type radicals, CARN in 200 μmol/L concentration tested was shown to exert a protective action on HA degradation. MTX was less effective than CARN in preventing HA degradation. Its ability to protect HA against radical degradation was evident only at the highest concentration of 400 μmol/L. In AA, carnosine significantly reduced TBARS and protein carbonyls in plasma, and also decreased the HPV of animals most effectively on the day 14.
  
  
  CONCLUSIONS
  CARN proved its inhibitory properties against degradation of HA solutions at experimental conditions in vitro and showed its beneficial efficiency in vivo. Moreover, it reduced also HPV, the clinical marker of inflammation in AA.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. frantisek.drafi@savba.sk
authors.forename: Frantisek
authors.initials: F
authors.lastname: Drafi
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
authors.forename: Katarina
authors.initials: K
authors.lastname: Valachova
authors.forename: Silvester
authors.initials: S
authors.lastname: Ponist
authors.forename: Danica
authors.initials: D
authors.lastname: Mihalova
authors.forename: Ivo
authors.initials: I
authors.lastname: Juranek
authors.forename: Alexander
authors.initials: A
authors.lastname: Boldyrev
authors.forename: Eva
authors.initials: E
authors.lastname: Hrabarova
authors.forename: Ladislav
authors.initials: L
authors.lastname: Soltes
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002336:Carnosine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D010084:Oxidation-Reduction; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018501:Antirheumatic Agents; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D002336:Carnosine; D006820:Hyaluronic Acid; D005978:Glutathione; D008727:Methotrexate