Concanavalin A (ConA) is a potent activator of immunocom- petent cells, particularly T lymphocytes, and is capable of inducing liver damage and hepatitis. Poly(ADP-ribose) poly- merase-1 (PARP-1) inhibitors have a pronounced protective effect in various experimental models of inflammation. Our study investigated the efficacy of PARP-1 inhibitors 4-hy- droxyquinazoline (4-HQ) and 3-aminobenzamide (3-ABA) in preventing DNA damage and preserving the viability of thymus and lymph node cells under the conditions of modeling immune-mediated hepatitis induced by Con A to determine their potential cytoprotective effect and ability to reduce the risk of developing immunoinflammatory damage. It was found that the administration of Con A leads to a significant increase in the integral DNA damage index (IDI) in immunocompetent cells compared to the control group. Thus, in thymus cells, the IDC increased from 0.36 ± 0.03 to 1.80 ± 0.24, in lymph node cells from 0.33 ± 0.07 to 1.82 ± 0.18. The proportion of cells with all classes of DNA damage, ranging from minimal to se- vere, significantly increased, indicating a profound disruption of the genome's structural integrity in immunocompetent cells. Prophylactic administration of 4-HQ and 3-ABA significantly reduced the levels of DNA damage: 4-HQ led to a decrease in IDI from 1.8 ± 0.24 to 0.39 ± 0.06, and under the action of 3-ABA to 0.83 ± 0.13 in thymus cells. A similar significant decrease in IDI was also found in lymph node cells. In ad- dition, under the action of 4-HQ and 3-ABA, the number of lymphocytes with severe damage (class 3 and 4) decreased, and those with intact DNA (class 0) increased. In addition, the use of the 3-ABA inhibitor led to an increase in the viability of immunocytes by reducing necrotic cell death, which indicates its pronounced cytoprotective effect. Thus, the study results show that Con A causes DNA damage in immunocompetent cells of both the central and peripheral immune system organs. 3-ABA and 4-HQ effectively reduce the degree of damage caused, demonstrating potential as therapeutic agents for preventing immunoinflammatory damage.