Because nephrotoxicity did not occur when PG was administered in an immediate release capsule, it seems unlikely that PG is solely responsible for the renal injury observed in dogs when receiving PG via enteric coated tablets. One hypothesis is that while PG enhances the gastrointestinal permeability of the MEDI7219 peptide, it may also allow other substances to cross the gastrointestinal membrane, such as inflammatory factors and uremic toxins. Leaky gut has been implicated as a source of inflammation in chronic kidney disease in humans . It is possible that enhanced gut permeability by PG in conjunction with a higher sensitivity to compounds requiring GSH-mediated detoxification may be responsible for the nephrotoxicity observed in dogs receiving PG via enteric coated tablets. Further studies are required to better understand the exact mechanism of PG-induced nephrotoxicity in dogs and the contribution of enteric coating as well as potential species differences. Additionally, non-targeted proteomics, lipidomic and metabolomics approaches can be employed to gain more comprehensive understanding of enteric-Figure . Cytotoxicity estimations in dog and human RPTECs after 48 h exposure to PG, GA, 4-O-methy-propyl gallate (4OMPG), and 4-O-methyl gallic acid (4OMGA). All human RPTEC determinations were from 5 independent experiments (2 different donors). For dog RPTECs PG and GA determinations were from 5 independent experiments, for 4OMPG and 4OMGA determinations were from 3 independent experiments (2 different donors). All experiments had 3 replicates per experiment. 4OMPG is a methylated form of GA and was used as a control compound.