Antioxidant effect of bisphosphonates and simvastatin on chondrocyte lipid peroxidation.
The objective of this study was to evaluate the effect of bisphosphonates (BPs) and simvastatin on chondrocyte lipid peroxidation. For this purpose, a flow cytometrical method using C11-BODIPY(581/591) was developed to detect hydroperoxide-induced lipid peroxidation in chondrocytes. Tertiary butylhydroperoxide (t-BHP) induced a time and concentration dependent increase in chondrocyte lipid peroxidation. Addition of a Fe2+/EDTA complex to t-BHP or hydrogen peroxide (H2O2) clearly enhanced lipid peroxidation. The lipophilic simvastatin demonstrated a small inhibition in the chondrocyte lipid peroxidation. None of three tested BPs (clodronate, pamidronate, and risedronate) had an effect on chondrocyte lipid peroxidation induced by t-BHP. However, when Fe2+/EDTA complex was added to t-BHP or H2O2, BPs inhibited the lipid peroxidation process varying from 25% to 58%. This study demonstrates that BPs have antioxidant properties as iron chelators, thereby inhibiting the chondrocyte lipid peroxidation. These findings add evidence to the therapeutic potential of bisphosphonates and statins in rheumatoid arthritis.
Dombrecht
E J
EJ
Immunology, Allergology and Rheumatology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
De Tollenaere
C B
CB
Aerts
K
K
Cos
P
P
Schuerwegh
A J
AJ
Bridts
C H
CH
Van Offel
J F
JF
Ebo
D G
DG
Stevens
W J
WJ
De Clerck
L S
LS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001896:Boron Compounds; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D004492:Edetic Acid; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005296:Ferrous Compounds; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D000077268:Pamidronate; D000068296:Risedronic Acid; D019821:Simvastatin / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000975:Antioxidants; D001896:Boron Compounds; C120421:C11-BODIPY(581-591); D004164:Diphosphonates; D005296:Ferrous Compounds; D004002:Clodronic Acid; C055526:Fe(II)-EDTA; D020122:tert-Butylhydroperoxide; D004492:Edetic Acid; D019821:Simvastatin; D006861:Hydrogen Peroxide; D000068296:Risedronic Acid; D012968:Etidronic Acid; D000077268:Pamidronate