Abstract
S-allylmercapto-N-acetylcysteine (ASSNAC) was shown in our previous study to activate Nrf2-mediated processes and increase glutathione level and resistance to oxidative stress in cultured endothelial cells. In this study, we explored the antioxidant protective effect of ASSNAC in Caenorhabditis elegans (C. elegans). Treatment of gst-4 reporter strain (CL2166) with increasing concentrations of ASSNAC (0.2 to 20 mM) for 24 hours and with ASSNAC (10 mM) for various time periods demonstrated a significant concentration- and time-dependent increase in Glutathione S-transferase (GST) gene expression (up to 60-fold at 20 mM after 24 hours). In addition, ASSNAC (2 mM; 24 hours) treatment of C. elegans strains N2 (wild type strain), gst-4 reporter (CL2166) and temperature sensitive sterile strain (CF512) significantly increased GST enzyme activity by 1.9-, 1.5- and 1.8-fold, respectively. ASSNAC (2.0 mM; 24 hours) increased the reduced glutathione content in N2 and CF512 strains by 5.9- and 4.9-fold, respectively. Exposure of C. elegans (N2 strain) to a lethal concentration of H2O2 (3.5 mM; 120 min) resulted in death of 88% of the nematodes while pretreatment with ASSNAC (24 hours) reduced nematodes death in a concentration-dependent manner down to 8% at 2.0 mM. C. elegans nematodes (strain CF512) cultured on agar plates containing ASSNAC (0.5 to 5.0 mM) demonstrated a significant increase in lifespan compared to control (mean lifespan 26.45 ± 0.64 versus 22.90 ± 0.59 days; log-rank p ≤ 0.001 at 2.0 mM) with a maximal lifespan of 40 versus 36 days. In conclusion, ASSNAC up-regulates the GST gene expression and enzyme activity as well as the glutathione content in C. elegans nematodes and thereby increases their resistance to oxidative stress and extends their lifespan.
Highlights
C. elegans transcription factor SKN-1 was shown to induce a phase II detoxification response, which protects against oxidative stress and is active in multiple longevity pathways [34,35]
Previous studies suggested that lifespan may be extended by enhanced resistance to oxidative stress [36] and herb mixture KPG-7 that contains several components exhibiting antioxidant activity has been shown to extend the lifespan of C. elegans [37]
Our study demonstrates the capacity of ASSNAC to increase the expression and activity of the antioxidant enzyme Glutathione S-transferase (GST) in a time- and concentration-dependent manner
Summary
Overproduction of reactive oxygen species (ROS) results in oxidative stress, shown to damage cellular structures, including membranes, lipids, proteins and DNA and plays a central. A recent study further showed that the natural thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) increase C. elegans oxidative stress resistance and extend their lifespan by modulating SKN-1/Nrf2 [13], while another study reported SAC antioxidant activity, with no effect on lifespan in C. elegans [14]. We demonstrated the ability of ASSNAC to increase expression of phase II detoxifying enzymes and glutathione level in cultured vascular endothelial cells, increasing the cellular protection against oxidative stress [15] and attenuating clinical symptoms of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis [16]. Our current study explores the ability of ASSNAC to increase glutathione content, GST gene expression and enzyme activity in C. elegans, which protect them against H2O2-induced death and extend their lifespan
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
