Arginase inhibition: A new treatment for preventing progression of established diabetic nephropathy

Hanning You, Ting Gao, Timothy K. Cooper, Sidney M. Morris, Alaa S Awad

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Our previous publication showed that inhibition of arginase prevents the development of diabetic nephropathy (DN). However, identification of targets that retard the progression of established DN-which is more clinically relevant-is lacking. Therefore, we tested the hypothesis that arginase inhibition would prevent the progression of established DN. Effects of arginase inhibition were compared with treatment with the angiotensin-converting enzyme inhibitor captopril, a current standard of care in DN. Experiments were conducted in Ins2Akita mice treated with the arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC) or captopril starting at 6 wk of age for 12 wk (early treatment) or starting at 12 wk of age for 6 wk (late treatment). Early and late treatment with BEC resulted in protection from DN as indicated by reduced albuminuria, histological changes, kidney macrophage infiltration, urinary thiobarbituric acidreactive substances, and restored nephrin expression, kidney nitrate/nitrite, kidney endothelial nitric oxide synthase phosphorylation, and renal medullary blood flow compared with vehicle-treated Ins2Akita mice at 18 wk of age. Interestingly, early treatment with captopril reduced albuminuria, histological changes, and kidney macrophage infiltration without affecting the other parameters, but late treatment with captopril was ineffective. These findings highlight the importance of arginase inhibition as a new potential therapeutic intervention in both early and late stages of diabetic renal injury.

Original languageEnglish (US)
Pages (from-to)F447-F455
JournalAmerican Journal of Physiology - Renal Physiology
Volume309
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Arginase
Diabetic Nephropathies
Captopril
Kidney
Albuminuria
Macrophages
Nitric Oxide Synthase Type III
Renal Circulation
Standard of Care
Nitrites
Angiotensin-Converting Enzyme Inhibitors
Nitrates
Cysteine
Phosphorylation
Wounds and Injuries

Keywords

  • ACEi
  • Arginase
  • Established diabetic nephropathy
  • Nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Arginase inhibition : A new treatment for preventing progression of established diabetic nephropathy. / You, Hanning; Gao, Ting; Cooper, Timothy K.; Morris, Sidney M.; Awad, Alaa S.

In: American Journal of Physiology - Renal Physiology, Vol. 309, No. 5, 01.01.2015, p. F447-F455.

Research output: Contribution to journalArticle

You, Hanning ; Gao, Ting ; Cooper, Timothy K. ; Morris, Sidney M. ; Awad, Alaa S. / Arginase inhibition : A new treatment for preventing progression of established diabetic nephropathy. In: American Journal of Physiology - Renal Physiology. 2015 ; Vol. 309, No. 5. pp. F447-F455.
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