title: Modulation of paraoxonase 1 (PON1) activity and protein N-homocysteinylation by bisphosphonates in rats.
abstract: OBJECTIVE
  Bisphosphonates are potent antiresorptive agents commonly used in the treatment of osteoporosis. As osteoporosis and atherosclerosis share some common risk factors and frequently coexist in the same patients, we examined the effect of bisphosphonates on paraoxonase 1 (PON1) - the high density lipoprotein-associated enzyme with potent anti-atherosclerotic activity.
  
  
  METHODS
  Bisphosphonates were administered orally to male adult rats for 4 weeks and then PON1 activity and some related biochemical parameters were measured in plasma.
  
  
  RESULTS
  Clodronate, alendronate, ibandronate and pamidronate reduced PON1 activity toward synthetic (paraoxon, phenyl acetate) and natural (homocysteine thiolactone) substrates. The most marked effect was observed in animals receiving ibandronate. In contrast, risedronate increased PON1 activity toward these 3 substrates and zoledronate increased PON1 activity toward phenyl acetate but had no effect on its activity toward paraoxon and homocysteine thiolactone. Bisphosphonates had no effect on total plasma homocysteine and protein-bound homocysteine thiolactone. In addition, total plasma cholesterol, HDL-cholesterol, plasma triglycerides and alanine aminotransferase activity did not differ between groups.
  
  
  CONCLUSIONS
  Bisphosphonates have differential effects on PON1 activity. Risedronate could be particularly useful in patients with high cardiovascular risk and PON1 deficiency. Bisphosphonates have no effect on plasma homocysteine and protein N-homocysteinylation as well as on the lipid profile.
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland. Electronic address: marta.rusek@umlub.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Rusek
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland. Electronic address: jola.racha@gmail.com.
authors.forename: Jolanta Elżbieta
authors.initials: JE
authors.lastname: Pastryk
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, 8b Jaczewskiego Street, 20-090 Lublin, Poland. Electronic address: jerzy.beltowski@umlub.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D004164:Diphosphonates / Q000737:chemistry / Q000494:pharmacology*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D008297:Male; D010261:Paraoxon / Q000633:toxicity; D010648:Phenylacetates / Q000097:blood; D017208:Rats, Wistar
chemical_list: D004164:Diphosphonates; D010648:Phenylacetates; D006710:Homocysteine; C007957:homocysteine thiolactone; D043303:Aryldialkylphosphatase; C025136:phenylacetic acid; D010261:Paraoxon
keywords: Bisphosphonates; Homocysteine; Homocysteine thiolactone; Osteoporosis; Paraoxonase 1; Protein N-homocysteinylation