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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Sex-Dependent Differences in Poly(ADP-Ribose)Polymerase 1 Activity of Rat Liver and Thymocyte Nuclei

Sex-dependent differences among therapeutic effects of PARP inhibitors were documented in treatment of various pathologies. The purpose of this study was to examine whether PARP 1 activity displays sexual dimorphism in liver cells and thymocytes of rat [1,2]. PARP 1 inhibition by benzamide (Bam) and ATP in liver and thymocyte nuclei after in vivo administration of cis-diammine-1,1-cyclobutanedicarboxylate platinum (cis-DDP) to animals was studied. Our data show that female thymocyte and liver nuclei, in contrast to male counterparts, exhibit organ-specific differences in PARP 1 activities. PARP 1 activity of female thymocyte nuclei was unaffected by Bam, while in liver nuclei it was suppressed by 45%. PARP 1 activity of the male rats liver nuclei was completely suppressed by Bam. It was demonstrated that in liver nuclei of male rats treated with cis-DDP PARP 1 activity decreased more than 3 times, whereas in liver nuclei of females it was suppressed only by 45%. In addition, the studies revealed that thymocyte nuclei of both sexes were more resistant to in vivo and ex vivo chemical interventions than liver nuclei. It was shown that in vivo administration of anti-cancer drug cis-DDP is capable to modulate PARP 1 inhibition by Bam in liver nuclei in sex-dependent manner which should be considered for improving therapeutic outcomes in adjuvant cancer chemotherapy by PARP 1 inhibitors.

References

    1. L. Virag, C. Szabo. (2002). The Therapeutic Potential of Poly(ADP-Ribose)Polymerase Inhibitors. Pharm. Reviews. 54(3). 375-418.

    2. D.J. Waxman, M.G. Holloway (2006). Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes. Mol. Pharmacol 76(2). 215-228.

Karine S. Matinyan
Anush L. Asatryan
Irina G. Artsruni
Arshak A. Karapetyan
Emil S. Gevorgyan

Department of Biophysics
Faculty of Biology
Yerevan State University
Yerevan, Armenia, 0025

Ph: (374)91795861
Email: karine.matinyan@ysu.am