A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat. Prostaglandins Other Lipid Mediat 2016 Sep;125:40-7
Date
07/20/2016Pubmed ID
27432695Pubmed Central ID
PMC5035206DOI
10.1016/j.prostaglandins.2016.07.003Scopus ID
2-s2.0-84979211632 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Cyclooxygenase (COX) and soluble epoxide hydrolase (sEH) inhibitors have therapeutic potential. The present study investigated efficacy of a novel dual acting COX-2/sEH inhibitor, PTUPB in type 2 diabetic Zucker Diabetic Fatty (ZDF) rats. Male ZDF rats were treated with vehicle or PTUPB (10mg/kg/d, i.p.) for 8 weeks. At the end of the 8-week experimental period, ZDF rats were diabetic (fasting blood glucose, 287±45mg/dL) compared to Zucker Diabetic Lean rats (ZDL, 99±6mg/dL), and PTUPB treatment improved glycemic status in ZDF rats (146±6mg/dL). Kidney injury was evident in ZDF compared to ZDL rats with elevated albuminurea (44±4 vs 4±2mg/d) and nephrinurea (496±127 vs 16±4μg/d). Marked renal fibrosis, tubular cast formation and glomerular injury were also present in ZDF compared to ZDL rats. In ZDF rats, PTUPB treatment reduced kidney injury parameters by 30-80% compared to vehicle. The ZDF rats also demonstrated increased inflammation and oxidative stress with elevated levels of urinary monocyte chemoattractant protein-1 excretion (862±300 vs 319±75ng/d), renal macrophage infiltration (53±2 vs 37±4/mm(2)) and kidney malondialdehyde/protein ratio (10±1 vs 5±1μmol/mg). PTUPB treatment decreased these inflammatory and oxidative stress markers in the kidney of ZDF rats by 25-57%. These data demonstrate protective actions of a novel dual acting COX-2/sEH inhibitor on the metabolic abnormalities and kidney function in ZDF rat model of type 2 diabetes.
Author List
Hye Khan MA, Hwang SH, Sharma A, Corbett JA, Hammock BD, Imig JDAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Epoxide Hydrolases
Kidney
Male
Metabolome
Oxidative Stress
Rats
Rats, Zucker
Sulfonamides
