l-Theanine ameliorates motor deficit, mitochondrial dysfunction, and neurodegeneration against chronic tramadol induced rats model of Parkinson's disease

Drug Chem Toxicol. 2022 Sep;45(5):2097-2108. doi: 10.1080/01480545.2021.1907909. Epub 2021 Jul 1.

Abstract

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disease, characterized by loss of dopaminergic neurons in substantia nigra, with deficiency of dopamine in the striatum. Tramadol is safe analgesic but long-term use confirmed to elevate oxidative stress, neuroinflammation, mitochondrial dysfunction, in brain leads to motor deficits. l-Theanine is an active constituent of green tea which prevents neuronal loss, mitochondrial failure and improves dopamine, gamma-aminobutyric acid (GABA), serotonin levels and in the central nervous system (CNS) via antioxidant, anti-inflammatory, and neuromodulatory properties. In the present study, tramadol was injected intraperitoneally to Wister rats for 28 days at a dose of 50 mg/kg. l-Theanine (25, 50, and 100 mg/kg) was administered orally 3 h before tramadol administration from day 14 to day 28. Behavioral analyses including rotarod, narrow beam walk, open field, and grip strength were used to evaluate motor coordination on a weekly basis. On the day 29, all Wistar rats were sacrificed and striatum homogenates were used for biochemical (lipid peroxidation, nitrite, glutathione, glutathione peroxidase activity, superoxide dismutase, catalase, mitochondrial complex I, IV, and cyclic adenosine monophosphate), neuroinflammatory markers (tumor necrosis factor-α, interleukin-1β, and interleukin-17), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Chronic tramadol treatment caused motor deficits reduced antioxidant enzymes level, increased striatal proinflammatory cytokines release, dysbalanced neurotransmitters, and reduced mitochondrial complex activity I, IV, and cAMP activity. However, l-theanine administration attenuated behavioral, biochemical, neuroinflammatory, neurotransmitters, and mitochondrial activity indicated it as a promising neuroprotective potential against degenerative changes in experimental model of PD.

Keywords: Parkinson’s disease; biochemical analysis; l-theanine; neuroinflammatory; neurotransmitters; tramadol.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Glutamates / metabolism
  • Glutamates / pharmacology
  • Mitochondria
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neurotransmitter Agents / metabolism
  • Oxidative Stress
  • Parkinson Disease* / drug therapy
  • Parkinson Disease* / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin
  • Tramadol* / metabolism
  • Tramadol* / pharmacology
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Antioxidants
  • Glutamates
  • Neuroprotective Agents
  • Neurotransmitter Agents
  • Serotonin
  • Tramadol
  • gamma-Aminobutyric Acid
  • theanine
  • Dopamine