Effect of Novel Compound LX519290, a Derivative of l-allo Threonine, on Antioxidant Potential in Vitro and in Vivo

Abstract

We investigated the antioxidative activity of LX519290, a derivative of l-allo threonine, in vitro and in vivo. To evaluate the antioxidative activity of LX519290, we performed several in vitro assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical-scavenging assays, a ferric reducing antioxidant power assay, cupric-reducing antioxidant capacity, and oxygen radical absorbance capacity assay) and evaluated inhibition against the generation of nitric oxide (NO) and reactive oxygen species (ROS) in murine macrophage (RAW264.7) cells. The results showed that LX519290 possessed very strong radical scavenging activity and reducing power, and inhibited NO and ROS generation in a dose-dependent manner without showing any cytotoxicity. LX519290 treatment also increased the total thiol content and glutathione S-transferases (GST) activities in RAW264.7 cells. Finally, we also determined whether LX519290 affects the mRNA levels of antioxidant enzymes in vitro and in vivo. The expression of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were markedly higher in the sample-treated group than in the oxidative stress group. LX519290 treatment also increased the transcriptional and translational activities of NF-E2-related factor-2 (Nrf-2) with corresponding increases in the transcriptional and translational activities of haeme oxygenase-1 (HO-1). Collectively, the data demonstrated that LX519290 has potent antioxidative activity, decreases NO and ROS generation, increases total thiol content and GST activities in RAW264.7 cells, and increases the transcriptional and translational levels of antioxidant enzymes in vitro and in vivo.

Optimization of Microwave-Assisted Extraction of Polysaccharides from Ulva pertusa and Evaluation of Their Antioxidant Activity

“…Macrophages are usually employed to evaluate the response to oxidative stress for host defense. Hydrogen peroxide (H 2 O 2 ) is commonly used for inducing oxidative stress-mediated cell injury in various kinds of cells [44,45]. We confirmed that 600 µM H 2 O 2 was sufficient to induce oxidative injury in RAW 264.7 macrophages.…”

DNA Protecting Activities of Nymphaea nouchali (Burm. f) Flower Extract Attenuate t-BHP-Induced Oxidative Stress Cell Death through Nrf2-Mediated Induction of Heme Oxygenase-1 Expression by Activating MAP-Kinases

“…It is well known that SOD1 is rapidly converted the O 2 − into H 2 O 2 which is subsequently detoxified to H 2 O by GPx and CAT [ 15 , 22 ]. Continuous exposure of oxidative stress may cause the damage of these primary antioxidant enzyme, which play a crucial role in cellular homeostasis during cell proliferation, and can develop various degenerative diseases [ 23 ]. In this study, NNFE treatment significantly increased both the mRNA and protein level of the antioxidant enzymes SOD1, CAT, and GPx-1 in RAW 264.7 cells and BV2 cells ( Figure 4 A,B, and Supplementary data Figure S10 , respectively), indicating that NNFE has the ability to maintain cellular homeostasis and to protect the cell from oxidative stress.…”

Reduction of Oxidative Stress through Activating the Nrf2 mediated HO-1 Antioxidant Efficacy Signaling Pathway by MS15, an Antimicrobial Peptide from Bacillus velezensis

“…MS15 treatment has been competent to enhance the translational and transcriptional levels of HO-1 and, in line with previous therapies, facilitates the Nrf-2 translocation in a concentration-reliant way into the nucleus. The process suggests that the antioxidant properties of MS15 are partly due to the concentration-dependent initiation of HO-1 in RAW 264.7 cells, controlled by dose-reliant activation of Nrf-2 [ 49 ]. However, the inhibition of the HO-1 role by HO-1 inhibitor considerably hindered those protective impacts of MS15 against H 2 O 2 .…”