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Flavonoid Naringenin Attenuates Oxidative Stress, Apoptosis and Improves Neurotrophic Effects in the Diabetic Rat Retina

Nutrients. 2017 Oct 24;9(10):1161. doi: 10.3390/nu9101161.

Abstract

Diabetic retinopathy (DR) is one of the leading causes of decreased vision and blindness worldwide. Diabetes-induced oxidative stress is believed to be the key factor that initiates neuronal damage in the diabetic retina leading to DR. Experimental approaches to utilize dietary flavonoids, which possess both antidiabetic and antioxidant activities, might protect the retinal damage in diabetes. The aim of this study was to investigate the potential protective effects of naringenin in the retina of streptozotocin-induced diabetic rats. Diabetic rats were orally treated and untreated with naringenin (50 mg/kg/day) for five weeks and retinas were analyzed for markers of oxidative stress, apoptosis and neurotrophic factors. Systemic effects of naringenin treatments were also analyzed and compared with untreated groups. The results showed that elevated levels of thiobarbituric acid reactive substances (TBARs) and decreased level of glutathione (GSH) in diabetic rats were ameliorated with naringenin treatments. Moreover, decreased levels of neuroprotective factors (Brain derived neurotrophic factor (BDNF)), tropomyosin related kinase B (TrkB) and synaptophysin in diabetic retina were augmented with naringenin treatments. In addition, naringenin treatment ameliorated the levels of apoptosis regulatory proteins; B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3 in the diabetic retina. Thus, the study demonstrates the beneficial effects of naringenin that possesses anti-diabetic, antioxidant and antiapoptotic properties, which may limit neurodegeneration by providing neurotrophic support to prevent retinal damage in diabetic retinopathy.

Keywords: apoptosis; diabetic retinopathy; flavonoid; naringenin; neurotrophic factor; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Blood Glucose / metabolism
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Retinopathy / drug therapy
  • Disease Models, Animal
  • Flavanones / pharmacology*
  • Flavonoids / pharmacology*
  • Glutathione / metabolism
  • Hypoglycemic Agents / pharmacology
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Retina / drug effects*
  • Retina / metabolism
  • Synaptophysin / blood
  • Thiobarbituric Acid Reactive Substances / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Bax protein, rat
  • Blood Glucose
  • Brain-Derived Neurotrophic Factor
  • Flavanones
  • Flavonoids
  • Hypoglycemic Agents
  • Nerve Tissue Proteins
  • Synaptophysin
  • Thiobarbituric Acid Reactive Substances
  • bcl-2-Associated X Protein
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • naringenin