WEDNESDAY, Dec. 19 (HealthDay News) -- The antidepressant paroxetine protects endothelial cells against hyperglycemia-induced injury, including reactive oxygen species (ROS) formation, according to a study published online Dec. 7 in Diabetes.
Using a phenotypic screen in endothelial cells exposed to elevated extracellular glucose, Domokos Gerö, M.D., from the University of Texas Medical Branch in Galveston, and colleagues assessed compounds that prevent hyperglycemia-induced reactive oxygen species formation without affecting cell viability. More than 6,000 clinically used drug-like and pharmacologically active compounds were examined. Follow-up studies focused on the antidepressant paroxetine.
The researchers found that paroxetine reduced formation of hyperglycemia-induced mitochondrial ROS, mitochondrial protein oxidation, and mitochondrial and nuclear DNA damage, but did not impair the electron transport or cellular bioenergetics of mitochondria. Paroxetine was the only serotonin reuptake blocker to prevent hyperglycemic endothelial cell injury. During in vitro hyperglycemia and ex vivo in a rat model of streptozotocin-induced diabetes, paroxetine maintained the ability of vascular rings to respond to the endothelium-dependent relaxant acetylcholine.
"Thus, the current work identifies a novel pharmacological action of paroxetine as a protector of endothelial cells against hyperglycemic injury and raises the potential of repurposing of this drug for the experimental therapy of diabetic cardiovascular complications," the authors write.
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