Edaravone attenuates hydroxyl radical stress and augmented angiotensin II response in diabetic rats.
Reactive oxygen species (ROS) potentiate angiotensin II (Ang II) responses in diabetic vasculature. However, superoxide scavengers partially restore this effect, suggesting free radicals other than superoxide could be involved. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is an antioxidant, which primarily scavenges hydroxyl radicals and is approved for use in stroke patients. Hence, to evaluate the role of hydroxyl radical stress in diabetic vascular complications, we studied the effect of edaravone (3 mgkg(-1), i.p., b.i.d.) treatment on Ang II responses in thoracic aorta isolated from streptozotocin (60 mgkg(-1) i.p.) induced 8 weeks diabetic male Sprague-Dawley rats. Ang II (10(-10) to 10(-6)M), tert-butyl hydro peroxide (tBHP; 10(-6) to 10(-2)M) or hydrogen peroxide (H2O2; 10(-6) to 10(-3)M) induced contractile response was significantly enhanced in aortic strips from diabetic as compared to control rats. Lipid peroxidation was significantly enhanced while the superoxide dismutase (SOD) and catalase activity was significantly lower in aorta of diabetic rats as compared to control rats. Acute (in vitro) exposure of edaravone (10(-5)M) to aortic strips from diabetic rats in the organ bath restored the augmented Ang II but not tBHP or H2O2-induced contractile response. In vivo edaravone (3mgkg(-1), i.p., b.i.d.) treatment for 2 weeks selectively attenuated the augmented Ang II- but not tBHP- or H2O2-induced contractile response. The enhanced systolic pressure, lipid peroxidation and the reduced SOD and catalase activity were restored to control values following 2 weeks edaravone treatment. From our results we infer that hydroxyl radical stress augments Ang II response in diabetic rat thoracic aorta and edaravone could be an ideal antioxidant adjuvant in the therapy of diabetic vascular complications.
Torrent Research Center, Gandhinagar, Gujarat, India.
Anuj Kumar
AK
Saini
Rashwin J
RJ
Patel
Shyam S
SS
Sharma
Arun Kumar
AK
H S
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D016166:Free Radical Scavengers; D000804:Angiotensin II; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D000077553:Edaravone; D000983:Antipyrine