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Abstract

The objective of the current study was to evaluate the potential of luteolin to mitigate the neurotoxic effects of OXL. Oxidative injury, inflammation, and mitochondrial dysfunction are the cardinal factors in OXL-triggered neuropathy. LUT modulates sensory and motor behavioral changes induced by OXL. Notably, LUT treatment significantly (p≤ 0.05) increased antioxidant activity by increasing paraoxonase-1 (PON-1) and heme oxygenase-1 (HO-1) levels, attenuating oxidative damage. Additionally, LUT inhibited neuroinflammation by repressing the levels of toll-like receptor-4 (TLR4) and intracellular adhesion molecule-1 (ICAM-1), while significantly increasing brain-derived neurotrophic factor (BDNF) and downregulating the relative gene expression level of mitogen-activated protein kinase 14 (MAPK-14). Moreover, LUT significantly reduced neuronal apoptosis (Caspase3; cysteine-aspartate-specific protease 3) and attenuated glial activation, while also restoring mitochondrial function. Furthermore, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in brain and sciatic nerve tissue, as well as glial fibrillary acidic protein (GFAP) immunohistochemical expression, were both markedly reduced by LUT. LUT protected neuronal structures from OXL-induced neuronal injury, as shown in histopathological examination. Lastly, both in vivo and in silico molecular docking findings confirmed the anti-inflammatory and neuroprotective effects of LUT, linked to MAPK-14 and GFAP. This study demonstrates that LUT provides a promising therapeutic effect in palliating OXL morbidity by targeting glial cells for neuropathy relief.

Keywords

GFAP, Glial cell, Luteolin, MAPK-14, Oxaliplatin, PON-1

Subject Area

Chemistry

Article Type

Article

First Page

1410

Last Page

1424

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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