A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat

Md Abdul Hye Khan, Sung Hee Hwang, Amit Sharma, John A. Corbett, Bruce D. Hammock, John D. Imig

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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/mm2) 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.

Original languageEnglish (US)
JournalProstaglandins and Other Lipid Mediators
DOIs
StateAccepted/In press - Jan 27 2016

Fingerprint

Epoxide Hydrolases
Metabolome
Cyclooxygenase 2
Rats
Kidney
Wounds and Injuries
Oxidative stress
Oxidative Stress
Chemokine CCL2
Macrophages
Prostaglandin-Endoperoxide Synthases
Medical problems
Malondialdehyde
Infiltration
Type 2 Diabetes Mellitus
Blood Glucose
Fasting
Fibrosis

Keywords

  • Diabetes
  • Diabetic nephropathy
  • Eicosanoid
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat. / Hye Khan, Md Abdul; Hwang, Sung Hee; Sharma, Amit; Corbett, John A.; Hammock, Bruce D.; Imig, John D.

In: Prostaglandins and Other Lipid Mediators, 27.01.2016.

Research output: Contribution to journalArticle

Hye Khan, Md Abdul ; Hwang, Sung Hee ; Sharma, Amit ; Corbett, John A. ; Hammock, Bruce D. ; Imig, John D. / A dual COX-2/sEH inhibitor improves the metabolic profile and reduces kidney injury in Zucker diabetic fatty rat. In: Prostaglandins and Other Lipid Mediators. 2016.
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