Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells

Abstract

BackgroundLow LET Ionizing radiation is known to alter intracellular redox balance by inducing free radical generation, which may cause oxidative modification of various cellular biomolecules. The extent of biomolecule-modifications/ damages and changes in vital processes (viz. cellular homeostasis, inter−/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant defence systems) are crucial which in turn determine fate of cells.ResultsIn the present study, we expended TLR expressing (normal/ transformed) and TLR null cells; and we have shown that mannan pretreatment in TLR expressing normal cells offers survival advantage against lethal doses of ionizing radiation. On the contrary, mannan pretreatment does not offer any protection against radiation to TLR null cells, NKE ρ° cells and transformed cells. In normal cells, abrupt decrease in mitochondrial membrane potential and endogenous ROS levels occurs following treatment with mannan. We intend to irradiate mannan-pretreated cells at a specific stage of perturbed mitochondrial functioning and ROS levels to comprehend if mannan pretreatment offers any survival advantage against radiation exposure to cells. Interestingly, pre-irradiation treatment of cells with mannan activates NFκB, p38 and JNK, alters mitochondrial physiology, increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial phospholipids and offers survival advantage in comparison to irradiated group, in TLR expressing normal cells.ConclusionThe study demonstrates that TLR and mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited by mannan.

WITHDRAWN: Prebiotic Mannan oligosaccharide pretreatment Improves Mice Survival Against Lethal Effects of Gamma Radiation by protecting GI Tract and Hematopoietic systems

“…Mitochondria is an important cell organelle that is both potential source as well as target of ROS. Correspondingly, under in vitro system, we have demonstrated that MOS counter IR induced ROS through alteration in mitochondrial physiology, increase in MnSOD and Cu/ZnSOD expression, and decrease in peroxidation of cardiolipin inside mitochondrial inner membrane [19] . As ageing progresses, there is more damage accumulation in mitochondria and there is decline in electron transport chain function.…”

“…Prebiotic MOS is reported to have bene cial effects in overall health of an organism, possess intestinal stimulatory capability, and immune modulation potential. And we have earlier reported in vitro radiation protection e cacy of MOS in normal cells with intact respiratory function [19]. This study focuses on demonstrating radioprotective effects of MOS, a prebiotic and understanding its role in reducing deleterious effects of TBI on hematopoietic and gastrointestinal system.…”

“…It stimulates the immune system of the host and has adsorbent capacity against toxins and it is non-toxic when administered orally, even in very large concentration [16][17]. Under in vitro conditions, we have demonstrated that MOS mediates alteration in mitochondrial physiology in immortalized normal cells and offer advantages in reducing biological effects of γ-radiation in vitro and thereby enhances cell survival [18][19]. TLRs have been reported to express in humans and mice [3,18,20], we intend to utilize the bene ts of MOS supplementation against radiation induced ARS.…”

Heat‐killed Salmonella typhimurium mitigated radiation‐induced lung injury

“…Other study indicated that acemannan acetyl, an extract from aloe vera gel, can reduce the γ‐radiation‐induced oxidative damage and haematopoietic injuries by free radical scavenging and microphage activation (secretes pro‐haematopoietic factors through TLR‐4) respectively . Sangurui S indicated that TLR and mitochondrial electron transport chain functions are inevitable in radioprotective efficacy exhibited by mannan . Our previous research found that HKMT exhibited radioprotective effects in vivo and in vitro through activating NF‐kB and MAPK signalling pathway .…”

Food Supplements to Mitigate Detrimental Effects of Pelvic Radiotherapy

“…Prebiotics Generally, little is known about immunomodulatory capacities of prebiotics in humans, and even less is reported in clinical radio-therapeutic settings. However, some preclinical studies showed possible immunosuppressive roles in cases of inflammatory bowel diseases [91,203,264]. The natural bioflavonoid propolis revealed successful, protective effects when mice were exposed to 9 Gy of γ rays, through an augmented activity of multiple immune cells [131,132].…”