Stable Gastric Pentadecapeptide BPC 157 Antagonizes Hydrogen Peroxide Induced Oxidative Stress in Drosophila melanogaster

In this work we hypothesize novel anti‐oxidative role for the stable gastric pentadecapeptide BPC 157 and we test this using a model organism, Drosophila melanogaster. BPC 157 was originally an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis where it largely interacts with NO‐system (Curr Pharm Des 2014;20(7):1126–35). BPC 157 is also thought to be a novel mediator of Robert's cytoprotection in rat studies, where its endothelium and mucosal protection is believed to be related to oxidative stress injury (Curr Pharm Des 2014;20(7):1126–35). To explore anti‐oxidative properties of BPC 157 we used the animal model of hydrogen peroxide (H2O2) induced oxidative stress in Drosophila melanogaster. Addition of increasing concentrations of H2O2 to regular Drosophila medium dose‐dependently shortened the lifespan of wild type (wt) Canton S Drosophila males (maximal survival on H2O2 is 8 days, compared to average lifespan of 80 days on regular fly food medium). Longevity of H2O2 fed males increased when they were grown on H2O2 medium supplemented with BPC 157. At 7 days, 54% of H2O2 wt males survived, compared to 84% of 0.6% H2O2 + 3.5 ng/ml BPC 157; at 12 days there was no survival on 0.6% H2O2, and 4% survival on 0.6% H2O2 + 3.5 ng/ml BPC 157. These results shows that; first, BPC 157 is biologically active in this invertebrate model system, and second, that that BPC 157 and H2O2 likely act on similar molecular pathways regulating longevity. Doses effective in promoting increased survival on H2O2 were extrapolated from biologically active doses in mammals. In conclusion, this suggests likely conservation of mechanisms by which BPC 157 antagonizes Reactive Oxidative Species (ROS) in invertebrates and vertebrates. Based on these intriguing observations we will investigate mechanisms by which BPC 157 exerts its anti‐oxidant actions. Because of the significant genetic and mechanistic conservation between Drosophila and vertebrates, discoveries made in this simple model organism will have significant translational potential and relevance for human health. Support or Funding Information University of Zagreb, Zagreb, Croatia (Grant number BM099)