ALL-TRANS RETINOIC ACID AFFORDS CYTOPROTECTION AGAINST RENAL TOXICANTS IN LLC-PK1 CELLS.

Ari Romans , R. Timothy Miller, Jessica M. Sapiro, Terrence J. Monks and Serrine S. Lau

ALL-TRANS RETINOIC ACID AFFORDS CYTOPROTECTION AGAINST RENAL TOXICANTS IN LLC-PK1 CELLS.

Oxidative stress results from a disruption of the cell’s antioxidant/prooxidant balance, in favor of the latter.  Initially, reactive oxygen species (ROS) disrupt cellular homeostasis by depleting cellular antioxidant and energy stores.  If ROS production continues unabated, damage to critical cellular constituents can occur.  When damage to the cell is too severe, cell death will occur.  The common toxicants hydrogen peroxide (H2O2), iodoacetamide (IDAM) and para-aminophenol (PAP) have been shown to produce toxicity in our porcine renal cell model of kidney injury (LLC-PK1) as assessed by the MTS cell viability assay, which measures mitochondrial dehydrogenase activity.  We found that pretreatment of cells with a biologically-active form of vitamin A, all-trans retinoic acid (ATRA; 25 mM, 24 hr), afforded protection against H2O2 (250 mM, 3 hr), PAP (150 mM, 3 hr) and IDAM (25 mM, 2 hr).  Specifically, cultures of LLC-PK1 cells exposed to H2O2 displayed a 50% reduction in cell viability.  However, pretreatment of cell cultures with ATRA improved the extent of cellular viability by 30%.  LLC-PK1 cell cultures exposed to PAP were ~ 60% viable.  In contrast, cell cultures pretreated with ATRA, were ~80% viable.  Finally, LLC-PK1 cell cultures exposed to IDAM were only 50% viable.  In stark contrast, cell cultures pretreated with ATRA were afforded near complete protection.  These data suggest that ATRA may provide an effective therapeutic intervention for renal injury induced by agents that produce cell death. (ES006694, ES016578 and ASPET)

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