PAR polymer metabolism play significant role in basal biological processes involved in cell death and survival pathways. PAR polymer turnover is maintained by coordinated interplay of enzymes responsible for PAR synthesis and degradation, poly(ADP- ribose)polymerase (PARP 1) and poly(ADP-ribose) glycohydrolase (PARG) correspondinglly. Nowadays, PARP 1 inhibitors entered into clinical treatment of cancer patients [1] and the search of less toxic PARP 1 inhibitors is in progress. It was documented, that natural product-tannic acid (TA) modulates poly(ADP-ribose) polymer (PAR) catabolism in the in vitro experimental settings [2]. However, little is known about the impact of TA on PARP1 activity and chromatin condensation in in vivo experimental settings. Herein, we examine whether intraperitoneal (i.p.) injection of TA to rats could influence PARP 1 activity in rat liver and thymocytes nuclei. The second goal of the study was investigation of the impact of TA on chromatin accessibility to Ca+2/Mg+2-dependent endonuclease, coming from the knowledge that PARP 1 determines chromatin condensation. Our data come to show, that i.p. injection of TA to rats suppressed PARP 1 activity both in thymocyte and liver nuclei and led to augmentation of liver chromatin resistance to DNA internucleosomal fragmentation. This data indicated on chromatin condensation in liver nuclei after administration of TA to rats. The in vivo treatment of rats with TA affects PARP 1 activity in thymocyte and liver nuclei in dose- and organ-specific manner. TA-induced condensation of liver nuclei chromatin could provide useful information about the type of cell death involved in TA-induced hepatotoxicity.

This work was supported by the RA MES State Committee of Science, in the frames of the research project № 18T-1F011.

References

1. C. Blenn, Ph. Wyrsch, F.R. Althaus. (2011). The Ups and Downs of Tannins as Inhibitors of Poly(ADP-Ribose)glycohydrolase. Molecules 16(2), 1854-1877. doi:10.3390/molecules16021854.

2. A.M. Czeh, Zs. Fabian, B. Sȕmegi, L. Scorrano. (2017). Poly(adenosine diphosphate-ribose)polymerase as therapeutic target: lessons learned from inhibitors. Oncotarget 8(30). 50221-50239. www.impactjournals.com/oncotarget