Evaluation of the modulation of nitric oxide synthase expression in the cerebellum of diabetic albino rats and the possible protective effect of ferulic acid

Acta Histochem. 2020 Dec;122(8):151633. doi: 10.1016/j.acthis.2020.151633. Epub 2020 Oct 10.

Abstract

Introduction: Diabetes mellitus is a multisystem disease. Oxidative stress and nitric oxide isoforms are involved in diabetic pathogenesis. Ferulic acid is a natural substance that is distributed broadly in plants with strong potent properties.

The aim of the research: This research was designed to study the possible protective role of ferulic acid on oxidative stress and different Nitric oxide synthase isoforms (NOS) in the cerebellum of streptozotocin-induced diabetic rats.

Materials and methods: Twenty-four albino male rats were randomly divided into equal four groups: control group, group 2 received ferulic acid orally (10 mg/kg), group 3 diabetic group, group 4 diabetic rats received ferulic acid. After 8 weeks, the left cerebellar hemisphere was taken for tissue homogenate for oxidative markers and real-time PCR for NOS isoforms. Paraffin sections of the right cerebellar hemisphere were stained with cresyl violet, Luxol fast blue and immnunohistochemically stained for neuronal NOS, inducible NOS and endothelial NOS.

Results: Degenerative changes were seen in the cerebella of the diabetic rats with significant elevation of Malondialdehyde, Nitric Oxide, and decrease of Superoxide dismutase levels. nNOS expression decreased and iNOS expression increased significantly. The ferulic acid-treated group showed a reduction of the degenerative changes in the cerebellum with significant improvement in oxidative stress marker, an increase of nNOS expression, and a decrease of iNOS expression.

Conclusions: Ferulic acid improves cerebellar functional and histopathological changes induced by diabetes which can be attributed mainly to its anti-oxidative effect and its ability to modulate NOS isoforms.

Keywords: Cerebellum; Diabetes; Ferulic acid; NO; NOS.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Blood Glucose / metabolism
  • Cerebellum / drug effects
  • Cerebellum / enzymology
  • Cerebellum / pathology
  • Coumaric Acids / pharmacology*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Gene Expression Regulation
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / genetics*
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / genetics*
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / genetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress
  • Rats
  • Rotarod Performance Test
  • Streptozocin
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Blood Glucose
  • Coumaric Acids
  • Hypoglycemic Agents
  • Insulin
  • Nitric Oxide
  • Malondialdehyde
  • Streptozocin
  • ferulic acid
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Nos3 protein, rat
  • Superoxide Dismutase