Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment.
Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by current treatments. Poly(ADP-ribose) polymerase (PARP) inhibitors ameliorate immune-mediated diseases in several experimental models, including RA, colitis, experimental autoimmune encephalomyelitis and allergy. Together these findings showed that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role in the regulation of immune responses and may represent a noble target for new therapeutic approaches in immune-mediated diseases. The effect of 3-aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) synthetase activity, was evaluated in a mouse model of adjuvant-induced arthritis (AIA) on pro-inflammatory cytokines, adhesion molecules, inflammatory mediators and chemokine production/expression in serum and knee joint. Histopathological examination was also done on joint section. Our data demonstrates that 3-AB, 10mg/kg, intraperitoneally (i.p.) significantly reduces pro-inflammatory cytokine (IL-17, TNF-α and IL-2) and chemokine (MCP-1 and MIP-2) production/expression, accompanied by amelioration of the disease as indicated by reduced paw swelling and arthritic scores and was associated with a significant reduction of VCAM-1 and ICAM-1 expression in the knee joint. Moreover, the expression of inflammatory mediators (iNOS, COX-2, MMP-2, MMP-9) and joint histological inflammatory damage was also markedly decreased. The results of this study suggest that PARP-1 inhibitor may play a role in the inflammatory arthritic process after administration of 3-AB may be a beneficial therapeutic approach.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia. Electronic address: s_fayazahmad@yahoo.com.
Sheikh Fayaz
SF
Ahmad
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.
Sabry M
SM
Attia
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia; Department of Cell Biology, National Research Centre, Cairo, Egypt.
Khairy M A
KM
Zoheir
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Abdelkader E
AE
Ashour
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, PO Box 11451, Riyadh, Saudi Arabia.
Saleh A
SA
Bakheet
D000818:Animals; D000843:Ankle Joint / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000235:genetics; D054426:Chemokine CXCL2 / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D014955:Wrist Joint / Q000473:pathology
D000893:Anti-Inflammatory Agents; D001549:Benzamides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; C025160:3-aminobenzamide; D005620:Freund's Adjuvant; D011065:Poly(ADP-ribose) Polymerases
3-Aminobenzamide; Adhesion molecules; Adjuvant induced arthritis; Chemokines; Inflammatory mediators; Poly(ADP-ribose) polymerase-1 inhibitor