Glycine Mitigates Lipopolysaccharide Induced Neurotoxicity via Inhibition of TLR-4 Signaling Pathway in Developing Mice Brain
DOI:
https://doi.org/10.52206/jsmc.2024.14.4.870Abstract
Background: Lipopolysaccharide (LPS) is an endotoxin of the gram-negative bacteria, playing a crucial role in systematic toxicity and cause neurotoxicity in immature brains. Glycine is non-essential amino acid, acting as a neurotransmitter, antioxidant and immune function regulator.
Objective: To investigate the potential use of glycine inhibition of TLR-4 receptor to reduce LPS induced neurodegeneration in the developing brain of post-natal day 7 (PND-7) mice.
Materials and Methods: A total of 12 PND-7 mice were included in this experimental study from Feb. 2023 to May 2023 at NMMRC, Peshawar. PND-7 mice were randomly distributed into four groups, a control group, a LPS group, LPS+Gly group and Gly group. LPS (250ìg /kg) was administered to LPS group. Glycine (1g/kg) was injected after LPS administration to LPS+Gly group and Gly group mice. After 4hr of the drug treatment, all the PND-7 mice were sacrificed for Western blot analysis. ImageJ software was used for the densitometry of the blots. One way ANOVA and post-hoc tukey tests through Prism graph-5 were applied for statistical analysis. P-value=0.05 was considered statistically significant.
Results: Significant differences were observed in the assessed markers in of PND 7 mice brains. Post hoc tukey test revealed significant changes (p<0.01) in the TLR-4 along with BAX, Casp-3, PARP-1and Bcl-2 levels in LPS group. However, significant decrease was observed in TLR-4 levels along with successful amelioration of BAX, Bcl-2, Casp-3 and PARP-1 level in LPS + Gly group as compared to LPS group.
Conclusion: Glycine administration significantly improved LPS induced neurodegeneration in brain of the PND-7 mice.
Keywords: Apoptosis, Caspase-3, Glycine, Lipopolysaccharide, Neurodegeneration, PARP-1, TLR-4 signaling pathway.
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