Protective effects of geraniol (a monoterpene) in a diabetic neuropathy rat model: attenuation of behavioral impairments and biochemical perturbations

J Neurosci Res. 2014 Sep;92(9):1205-16. doi: 10.1002/jnr.23393. Epub 2014 Apr 17.

Abstract

Involvement of oxidative stress, inflammatory response, and mitochondrial dysfunction in the development of diabetic neuropathy (DN) is well appreciated. The present study examines the potential of geraniol (GE), a well-known phytoconstituent commonly found in lemon, spices, rose oil, etc., to attenuate DN-associated oxidative/nitrosative stress by employing a streptozotocin (STZ) diabetic rat model. STZ-induced diabetic rats provided with oral supplements of GE (100 mg/kg bw/day, 8 weeks) exhibited significant improvement in tail-flick latency (sensory function) and the narrow beam test (motor function). Terminally, elevated levels of oxidative markers (reactive oxygen species, malondialdehyde, hydroperoxides) in cytosol of the sciatic nerve (SN) and in selected regions of the brain of diabetic rats were markedly reduced by GE supplements. Furthermore, GE significantly diminished the levels of protein carbonyls (a measure of protein oxidation) and nitrites in diabetic rats. In addition, in mitochondria, GE supplements restored the activities of enzymes, such as complexes I-III, succinate dehydrogenase, and citrate synthase, in brain regions of diabetic rats, with a concomitant reduction in the levels of oxidative markers. GE significantly lowered the enhanced cytosolic calcium levels and acetylcholinesterase activity in the SN and the brain regions of diabetic rats. Depleted dopamine levels evident in the SN and the cortex/striatum among diabetic rats were restored by GE. From our data, we hypothesize that GE may be a promising therapeutic candidate in the management of DN in humans. Further understanding of the molecular mechanisms of its neuromodulatory effects is essential in order to exploit its therapeutic efficacy.

Keywords: behavioral tests; brain regions; diabetic rat; mitochondria; oxidative stress; sciatic nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Administration, Oral
  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / pathology
  • Disease Models, Animal
  • Hydrogen Peroxide / metabolism
  • Hyperalgesia / drug therapy*
  • Hypoglycemic Agents / administration & dosage*
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Oxidoreductases / metabolism
  • Psychomotor Disorders / drug therapy
  • Psychomotor Disorders / etiology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Terpenes / administration & dosage*

Substances

  • Acyclic Monoterpenes
  • Hypoglycemic Agents
  • Reactive Oxygen Species
  • Terpenes
  • Malondialdehyde
  • Hydrogen Peroxide
  • Oxidoreductases
  • geraniol