Protective Effects of Naringenin in Cardiorenal Syndrome

J Surg Res. 2016 Jun 15;203(2):416-23. doi: 10.1016/j.jss.2016.03.003. Epub 2016 Mar 10.

Abstract

Background: Cardiorenal syndrome is a complicated and bidirectional interrelationship between the heart and kidneys. Naringenin (NG) is a naturally occurring flavonoid possessing various biological and pharmacological properties.

Materials and methods: We tested whether NG could improve cardiac and renal function in a rat model of cardiorenal syndrome.

Results: The results showed that NG-attenuated cardiac remodeling and cardiac dysfunction in rats with cardiorenal syndrome, as evidenced by decrease of left ventricle weight (LVW), increase of body weight (BW), decrease of LVW/BW, decrease of concentrations of serum creatinine, blood urea nitrogen, type-B natriuretic peptide, aldosterone, angiotensin (Ang) II, C-reactive protein, and urine protein, increase of left ventricular systolic pressure and falling rates of left ventricular pressure (dp/dtmax), and decrease of left ventricular diastolic pressure, left ventricular end-diastolic pressure, and -dp/dtmax. NG significantly inhibited the increase of lipid profiles including low-density lipoprotein, TC, and TG in rats. In addition, NG significantly inhibited the increase of cardiac expression of IL-1β, IL-6, and interferon γ. Moreover, NG decreased malonaldehyde level, increased superoxide dismutase activity and glutathione content in rats, and increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunit of γ-glutamylcysteine ligase (GCLc) in rats and Ang II-treated cardiac fibroblasts. Inhibition of Nrf2 and glutathione synthesis significantly suppressed NG-induced decrease of ROS level. Inhibition of Nrf2 markedly suppressed NG-induced increase of GCLc expression in Ang II-treated cardiac fibroblasts.

Conclusions: The data provide novel options for therapy of patients and new insights into the cardioprotective effects of NG in cardiorenal syndrome.

Keywords: Cardiorenal syndrome; GCLc; Naringenin; Nrf2; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Biomarkers / metabolism
  • Cardio-Renal Syndrome / drug therapy*
  • Cardio-Renal Syndrome / metabolism
  • Cardio-Renal Syndrome / pathology
  • Cardio-Renal Syndrome / physiopathology
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Oxidative Stress / drug effects
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Treatment Outcome

Substances

  • Antioxidants
  • Biomarkers
  • Flavanones
  • naringenin