In vitro stimulatory effect of N‐acetyl tryptophan‐glucopyranoside against gamma radiation induced immunosuppression

Abstract

Radiation-induced manifestations like free radical burst, oxidative damage and apoptosis leading to cell death. In present study, N-acetyl tryptophan glucopyranoside (NATG) was assessed for its immune-radioprotective activities using J774A.1 cells. Clonogenic cell survival, cell cycle progression and cytokines i.e. IFN-γ, TNF-α, IL-2, IL-10, IL-12, IL-13 and IL-17A expression were evaluated in irradiated and NATG pretreated cells using clonogenic formation ability, flow cytometry and ELISA assay. Results indicated that 0.25μg/ml NATG exhibited maximum radioprotection against gamma-radiation (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus irradiated cells showed significant elevation in IFN-γ (∼38.2%), IL-17A (∼53.7%) and IL-12 (∼58.8%) expression as compared to only irradiated cells. Conversely, significant decrease in TNF-α (∼21.6%), IL-10 (∼31.2%), IL-2 (∼23.7%) and IL-13 expression (∼17.8%) were observed in NATG pretreated plus irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment to irradiated J774A.1 cells, stimulate Th while diminish Th cytokines that contributes to radioprotection.

Amelioration of Radiation-Induced Cell Death in Neuro2a Cells by Neutralizing Oxidative Stress and Reducing Mitochondrial Dysfunction Using N-Acetyl-L-Tryptophan

“…These findings suggested the excellent radioprotective activity of N-acetyl-L-tryptophan in the cells of neuronal origin. N-acetyl-L-tryptophan glucoside (NATG), a close glucosidic derivative of NAT, has been reported for its radioprotective properties in the murine macrophage j774A.1 cells and mice against lethal radiation dose, supported the present study [ 38 , 39 ]. Ionizing radiation augments oxidative stress via the induction of free radicals in the cellular milieu that causes direct or indirect DNA damage, leading to genomic instability [ 40 ].…”

“…These observations suggest a priming phenomenon initiating in Neuro2a cells after L-NAT administration, increasing hydrogen peroxide and other ROS/RNS levels in the cellular milieu. The priming phenomena/intrinsic mild oxidative stress may further activate the endogenous antioxidant machinery to combat oxidative stress in the advance that may likely arise in the near future due to irradiation, as shown in the previous study [ 21 , 38 , 39 ]. Similarly, L-NAT treatment increased mild hyperpolarization of mitochondrial membrane, antioxidant enzyme activity such as catalase, SOD, MPO, and non-enzymatic factors, such as GSH and nitrite levels (RNS) compared to control in Neuro2a cells, were confirm the effect of intrinsic oxidative stress on the activation of endogenous antioxidant machinery (Figures 8 and 10 ).…”

N‐acetyl‐l‐tryptophan (NAT) ameliorates radiation‐induced cell death in murine macrophages J774A.1 via regulating redox homeostasis and mitochondrial dysfunction

“…Some novel secondary metabolites that is, semiquinone glucoside (SQGD) and N‐acetyl‐ l ‐tryptophan glucoside (NATG) of radioresistant bacterial origin have been evaluated for their radioprotective and immunoprotective activities against gamma radiation‐induced oxidative stress. [ 23,24,28–33 ] In the present study, NAT, a secondary metabolite, isolated and characterized from the radioresistant bacterium Bacillus sp. INM‐1 was assessed for its radioprotective efficacy using murine macrophage J774A.1 cells.…”