Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment

• We investigated the possible anti-arthritic effects of the PARP-1 inhibitor.
• 3-Aminobenzamide (3-AB) inhibitory activity was evaluated in a mouse model.
• It indicates that 3-AB shows anti-arthritic activity.
• 3-AB markedly decreased inflammatory mediators and adhesion molecules.
• 3-AB significantly reduced chemokine expression.

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, 10 mg/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.