[THE EFFECT OF OF POLY(ADP-RIBOSE) POLYMERASE INHIBITOR 4-HYDROXY-QUINAZOLINE ON DEATH OF IMMUNE CELLS UNDER IMMUNE COMPLEX-MEDIATED INJURY IN MICE].

Abstract

The influence of poly(ADP-ribose) polymerase (PARP) in- hibitor 4-hydroxyquinazoline (4-HQ) on the level of DNA damage and on the death of thymic and lymph node cells in mouse model of immune complex injury was investigated to reveal its possible cytoprotective effect. As shown by comet assay, DNA damage index of immune cells was increased 4,0 times in mice with immune complex-mediated pathology induced by a long-term immunization of CBA mice with bovine serum albumin (BSA), P<0,001. The percentage of thymic cells with strong DNA damage was increased to 77% under immunization (compared to 1,5% in control mice) and the percentage of such cells from lymph nodes was increased to 80% (compared to 0% in control), in both cases P< 0,001. Genotoxic stress was reduced by treatment of immunized mice with 4-HQ: the percentage of lymphocytes with strong DNA damage was significantly decreased that promoted increase in the amount of cells having intact DNA. PARP inhibition exerted a strong cytoprotective effect: viability of thymus and lymph node cells was increased mainly due to reduced level of necrosis. So, our results suggest that PARP may be involved in thymic and lymph node cell damage in immune complex mediated pathology and give evidence that inhibition of this enzyme may constitute a perspective target in immune complex diseases prevention and therapy.