Reversal of oxidative stress in endothelial cells by controlled release of adiponectin.
Hyperglycemia causes endothelial dysfunction due to its effect on increasing reactive oxygen species (ROS). Adiponectin (Adp) has been reported to suppress hyperglycemia-associated ROS generation. It was hypothesized that administering globular adiponectin (gAdp) via injectable biodegradable thermosensitive triblock copolymer might effectively reduce ROS generation in endothelial cells. In this study, gAdp was incorporated into and released from the polymer gel. The released gAdp was further investigated by comparing it with the intact gAdp with regard to the efficiency in reducing ROS and activating cAMP. The released gAdp effectively suppressed excess ROS production in the in vitro endothelial cell culture model under high-glucose condition via cAMP/PKA pathway. These data provide a rationale for developing controlled release dosage form of gAdp as a therapeutic tool for oxidative stress-related pathology in patients with diabetes.
Mossalam
Mohanad
M
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
Jeong
Ji-Hoon
JH
Abel
E Dale
ED
Kim
Sung Wan
SW
Kim
Yong-Hee
YH
D052242:Adiponectin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003692:Delayed-Action Preparations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism
D052242:Adiponectin; D003692:Delayed-Action Preparations; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000242:Cyclic AMP; D005947:Glucose