Effects of bee venom on protease activities and free radical damages in synovial fluid from type II collagen-induced rheumatoid arthritis rats.
The effect of bee venom acupuncture (BVA) (api-toxin) on the development of type II collagen (CII)-induced arthritis (CIA) in rats has been studied. We have compared the levels of activity of a comprehensive range of cytoplasmic, lysosomal and matrix protease types, together with the levels of free radical-induced protein damage (determined as protein carbonyl derivative) in synovial fluid from CIA-treated, BVA-treated and normal rats. Many protease types showed significantly increased activity in CIA compared with normal rats. BVA (5 and 10 microl/100g) significantly reduced these enzyme activities by some 80% each, but levels of plasma proteases activity (including those enzyme types putatively involved in the immune response, such as dipeptidyl aminopeptidase IV and proline endopeptidase) in CIA, BVA (5 microl/100g)-treated and normal plasma samples were not significantly different. The level of free radical induced damage to synovial fluid proteins was approximately three-fold higher in CIA compared with normal rats. However, BVA (5 microl/100g) significantly decreased the level of reactive oxygen free radical species (ROS) induced oxidative damage to synovial fluid proteins. It was concluded that activation of proteolytic enzymes and free radicals are likely to be of equal potential importance as protein damaging agents in the pathogenesis of rheumatoid arthritis (RA), and the development of novel therapeutic strategies for the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of enzymatic mechanistic types (cysteine, serine, metallo proteinases and peptidases). In conclusion, BVA is considered to be an effective RA modulator, inhibiting protease activities and removing ROS.
Suh
Seok-Jong
SJ
Molecular and Cellular Glycobiology Unit, Department of Biological Science, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi 440-746, Republic of Korea.
Kim
Kap-Sung
KS
Kim
Min-Jung
MJ
Chang
Young-Chae
YC
Lee
Seung-Duk
SD
Kim
Myung-Sunny
MS
Kwon
Dae Young
DY
Kim
Cheorl-Ho
CH
D026881:Acupuncture; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D001514:Bee Venoms / Q000494:pharmacology*; D024043:Collagen Type II; D003593:Cytoplasm / Q000201:enzymology; D005609:Free Radicals / Q000737:chemistry*; D008247:Lysosomes / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013582:Synovial Fluid / Q000187:drug effects* / Q000201:enzymology
D001514:Bee Venoms; D024043:Collagen Type II; D005609:Free Radicals; D010447:Peptide Hydrolases