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

Abstract

<jats:p> 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. </jats:p>

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

“…Therefore, we assessed the effects of pomegranate juice treatment on the antioxidant defense system in the midbrain. Although many authors have shown the decrease in GSH level and/or antioxidant enzymes activity in this brain area of rats exposed to rotenone [31,[40][41][42][47][48][49][50], in our experiment, these markers were not affected significantly by rotenone administration. Differences in the response can be associated with the higher doses of rotenone, ranging between 1.5 mg/kg b.w.…”

“…We did not find any significant difference in inflammatory response among the groups, but it might be related to the moderate level of rotenone-induced lipid peroxidation. Several authors have reported an increased expression of proinflammatory cytokines, including TNF-α and/or level of total NO accompanied by very high (3-5-fold) increase in MDA level in the midbrain of animals administered with rotenone [42,50,57].…”

Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease

“…Agmantine, a metabolite derived from arginine decarboxylation that is found throughout the brain and particularly in the hypothalamus, is capable of selectively blocking neurotransmission through NMDA receptors in specific areas of the brain, like the hippocampus, and it has been shown to attenuate nitric oxide production, oxidative stress, and glutamate-dependent excitotoxicity in animal models of dyskinesia and hyperalgesia [250]. Furthermore, intra-peritoneal supplementation with agmantine reduces neuronal damage, atrogliosis, lipid peroxidation and production of IL-1β and TNF-α in animal models of PD [251]. Additionally, there is evidence that agmantine may have anti-depressant, anxiolytic, and anti-convulsive properties, derived from its capacity to bind to alpha-2 adrenergic receptors, nicotinic and muscarinic acetylcholine receptors, as well as alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors [250].…”

Unraveling the neuroprotective effect of Tinospora cordifolia in Parkinsonian mouse model through proteomics Approach.

“…Recent studies revealed that Rotenone (ROT), a pesticide which is also an inhibitor of mitochondrial complex-I; when administrated consistently, recapitulated PD's features like reactive oxygen species (ROS) generation, degeneration of the nigrostriatal DAergic system etc. [8][9][10]. As PD advances, the death of DAergic neurons surges and these neurons don't have potency to regenerate.…”