Chronic Administration of S-Allylcysteine Activates Nrf2 Factor and Enhances the Activity of Antioxidant Enzymes in the Striatum, Frontal Cortex and Hippocampus

Abstract

Oxidative stress plays an important role in neurodegenerative diseases and aging. The cellular defense mechanisms to deal with oxidative damage involve the activation of transcription factor related to NF-E2 (Nrf2), which enhances the transcription of antioxidant and phase II enzyme genes. S-allylcysteine (SAC) is an antioxidant with neuroprotective properties, and the main organosulfur compound in aged garlic extract. The ability of SAC to activate the Nrf2 factor has been previously reported in hepatic cells; however this effect has not been studied in normal brain. In order to determine if the chronic administration of SAC is able to activate Nrf2 factor and enhance antioxidant defense in the brain, male Wistar rats were administered with SAC (25, 50, 100 and 200 mg/kg-body weight each 24 h, i.g.) for 90 days. The activation of Nrf2, the levels of p65 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as the activities of the enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) were evaluated in the hippocampus, striatum and frontal cortex. Results showed that SAC activated Nrf2 factor in the hippocampus (25-200 mg/kg) and striatum (100 mg/kg) and significantly decreased p65 levels in the frontal cortex (25-200 mg/kg). On the other hand, SAC increased GPx, GR, CAT and SOD activities mainly in the hippocampus and striatum, but it did not change GST activity. Finally, no changes were observed in 8-OHdG levels mediated by SAC in any brain region, but the hippocampus showed a major level of 8-OHdG compared with the striatum and frontal cortex. All these results suggest that in the hippocampus, the observed increase in the activity of antioxidant enzymes could be associated with the ability of SAC to activate Nrf2 factor; however, a different mechanism could be involved in the striatum and frontal cortex, since no changes were found in Nrf2 activation and p65 levels.

NMDA Receptor-Mediated Excitotoxicity Is Involved in Neuronal Apoptosis and Cognitive Impairment Induced by Chronic Hypobaric Hypoxia Exposure at High Altitude

“…The expression and oxidative stress of Caspase-3 and glutamate receptors in the hippocampal and cortical tissues were consistent, indicating that there was no regional difference in the damage of chronic hypobaric hypoxia to the brain tissue. This is consistent with other reports (Franco-Enzástiga et al, 2017;Thomas et al, 2017;Ko et al, 2019).…”

The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and multidrug-resistant human cancer cells by altering mitochondrial permeability

“…Aged garlic extract (AGE) has been shown to possess various water-soluble organic sulfur compounds, such as SAC, SAMC and S-1-propenylcysteine by unique manufacturing process (15). AGE possesses greater antioxidant activity than fresh garlic by scavenging reactive oxygen species (ROS), enhancing the activity of cellular antioxidant enzymes (e.g., superoxide dismutase, catalase and glutathione peroxidase), mainly observed following the administration of SAC in vivo (16), and increasing glutathione levels in cells (17)(18)(19). Several studies on both animals and humans have shown that AGE contributes to a reduced risk of cancer (20,21), cardiovascular disease (22)(23)(24), Alzheimer's disease and other age-related degenerative conditions (19,25).…”

Garlic and its Active Compounds: A Novel Strategy to Fight Diseases Through Modulating Biological Activities

“…25 Another finding reported that S-allylcysteine showed increased glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase activities and increase in the activity of antioxidant enzymes. 26 A study was performed based on gentamicin toxicity in rats and result confirmed that significant increase in myeloperoxidase and lipid peroxidation levels was observed, that was reduced after treatment with diallyl sulfide. Moreover, gentamicin-induced rats showed a significant decrease in the activities of various antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and Quinone reductase that was increased after treatment with diallyl sulfide.…”