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Anti-Inflammatory Action of Sitagliptin and Linagliptin in Doxorubicin Nephropathy

Chor Ho Jo1, Sua Kim1, Joon-Sung Park2

  • 1Institute of Biomedical Science, Hanyang University College of Medicine, Seoul, Republic of Korea.

Kidney & Blood Pressure Research
|June 19, 2018
PubMed
Abstract

Insights

Dipeptidyl peptidase-4 (DPP4) inhibitors like sitagliptin and linagliptin suppress NLRP3 inflammasome activation in doxorubicin-induced kidney injury. These DPP4 inhibitors may offer protective effects against non-diabetic proteinuric kidney diseases.

Area of Science:

  • Nephrology
  • Pharmacology
  • Immunology

Background:

  • Dipeptidyl peptidase-4 (DPP4) inhibitors are recognized for protecting against diabetic kidney disease, potentially through reduced oxidative stress and inflammation.
  • Their role in non-diabetic proteinuric kidney diseases remains unclear.

Purpose of the Study:

  • To investigate the effects of DPP4 inhibitors (sitagliptin and linagliptin) on doxorubicin-induced nephropathy in rats.
  • To explore the underlying mechanisms, including oxidative stress and NLRP3 inflammasome activation.

Main Methods:

  • Male Sprague-Dawley rats underwent uninephrectomy and were treated with doxorubicin.
  • Rats received either sitagliptin or linagliptin daily via oral gavage for six weeks.
  • Kidney injury, inflammation, fibrosis, and gene expression (NLRP3 inflammasome, oxidative stress markers) were assessed.

Main Results:

  • Doxorubicin induced hypertension and proteinuria. Linagliptin reduced blood pressure, while sitagliptin ameliorated tubulointerstitial injury and fibrosis.
  • Both sitagliptin and linagliptin suppressed NLRP3 inflammasome activation (NLRP3, caspase-1, ASC, IL-1β).
  • Sitagliptin reduced oxidative stress markers (gp91phox, p47phox, p67phox), whereas linagliptin decreased IL-6 levels.

Conclusions:

  • NLRP3 inflammasome activation is implicated in doxorubicin-induced nephropathy.
  • DPP4 inhibitors effectively suppress NLRP3 inflammasome activity in this model.
  • DPP4 inhibitors may exert protective effects independent of or in conjunction with modulating NADPH oxidase 2-related oxidative stress.
Keywords:
Blood pressureDipeptidyl peptidase-4DoxorubicinInflammasomeNADPH oxidase

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