Original Article The Thromboxane Receptor Antagonist S18886 Attenuates Renal Oxidant Stress and Proteinuria in

Arachidonic acid metabolites, some of which may activate thromboxane A2 receptors (TPr) and contribute to the development of diabetes complications, including nephrop-athy, are elevated in diabetes. This study determined the effect of blocking TPr with S18886 or inhibiting cyclooxy-genase with aspirin on oxidative stress and the early stages of nephropathy in streptozotocin-induced diabetic apoli-poprotein E/ mice. Diabetic mice were treated with S18886 (5 mg kg1 day1) or aspirin (30 mg kg1 day1) for 6 weeks. Neither S18886 nor aspirin affected hyperglycemia or hypercholesterolemia. There was intense immunohistochemical staining for nitrotyrosine in diabetic mouse kidney. In addition, a decrease in manganese super-oxide dismutase (MnSOD) activity was associated with an increase in MnSOD tyrosine-34 nitration. Tyrosine nitra