Neuroprotective effect of agmatine (decarboxylated l-arginine) against oxidative stress and neuroinflammation in rotenone model of Parkinson's disease

Hum Exp Toxicol. 2019 Feb;38(2):173-184. doi: 10.1177/0960327118788139. Epub 2018 Jul 13.


Parkinson's disease (PD) is the second most common age-related neurodegenerative disease after Alzheimer's disease, characterized by loss of dopaminergic neurons in substantia nigra pars compacta, accompanied by motor and nonmotor symptoms. The neuropathological hallmarks of PD are well reported, but the etiology of the disease is still undefined; several studies assume that oxidative stress, mitochondrial defects, and neuroinflammation play vital roles in the progress of the disease. The current study was established to investigate the neuroprotective effect of agmatine on a rotenone (ROT)-induced experimental model of PD. Adult male Sprague Dawley rats were subcutaneously injected with ROT at a dose of 2 mg/kg body weight for 35 days. Agmatine was injected intraperitoneally at 50 and 100 mg/kg body weight, 1 h prior to ROT administration. ROT-treated rats that received agmatine showed better performance on beam walking and an elevated number of rears within the cylinder test. In addition, agmatine reduced midbrain malondialdehyde as an indication of lipid peroxidation, pro-inflammatory cytokines including tumor necrosis factor alpha and interleukin-1β, and glial fibrillary acidic protein. Moreover, agmatine was responsible for preventing loss of tyrosine hydroxylase-positive neurons. In conclusion, our study showed that agmatine possesses a dose-dependent neuroprotective effect through its antioxidant and anti-inflammatory activities. These findings need further clinical investigations of agmatine as a promising neuroprotective agent for the future treatment of PD.

Keywords: Parkinson’s disease; agmatine; neuroinflammation; oxidative stress; rotenone.

MeSH terms

  • Agmatine / pharmacology
  • Agmatine / therapeutic use*
  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / metabolism
  • Rats, Sprague-Dawley
  • Rotenone
  • Tyrosine 3-Monooxygenase / metabolism


  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Neuroprotective Agents
  • Rotenone
  • Malondialdehyde
  • Agmatine
  • Tyrosine 3-Monooxygenase
  • Glutathione