D-Ribose-L-cysteine attenuates lipopolysaccharide-induced memory deficits through inhibition of oxidative stress, release of proinflammatory cytokines, and nuclear factor-kappa B expression in mice.

Abstract

D-Ribose-L-cysteine (DRLC), an analog of cysteine that boosts glutathione (GSH) content, has been reported to mitigate oxidative stress-mediated diseases. This study seeks to evaluate the effects of DRLC on memory deficits and the biochemical and histo-morphological changes induced by lipopolysaccharide (LPS) in mice. Male Swiss mice (n = 10) were pre-treated orally with three doses of DRLC (25 mg/kg, 50 mg/kg, and 100 mg/kg), donepezil (1 mg/kg), or vehicle (saline) for 30 min prior to the intraperitoneal injection of LPS (0.25 mg/kg) daily for 7 days. Memory functions were evaluated using the Y-maze, object recognition, and social recognition tests. The specific brain regions (prefrontal cortex and hippocampus) were evaluated to determine oxidative stress biomarkers (malondialdehyde, GSH, and catalase), acetyl-cholinesterase activity, proinflammatory cytokines (tumor necrosis factor-α and interleukin-6), expression of nuclear factor-kappa B (NF-κB), and neuronal cell morphology. DRLC (25-100 mg/kg) reversed the memory deficits in the LPS-treated mice (p < 0.05). The increased oxidative stress and proinflammatory cytokines in the brain regions of the LPS-treated mice were significantly (p < 0.05) reduced by DRLC. DRLC (50 mg/kg and 100 mg/kg) also reduced acetyl-cholinesterase activity and decreased NF-κB expression in the brains of LPS-treated mice. Finally, it attenuated the cytoarchitectural distortions and loss of neuronal cells of the prefrontal cortex and hippocampus that were induced by LPS in mice. The results of this study suggest that DRLC attenuates memory deficit induced by LPS in mice through mechanisms related to the inhibition of oxidative stress, release of proinflammatory cytokines, and expression of NF-κB in mice.

• Authors: Osagie Emokpae, Benneth Ben-Azu, Abayomi M Ajayi, Solomon Umukoro
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 393 Issue 5 Pg. 909-925 (05 2020) ISSN: 1432-1912 [Electronic] Germany
• PMID: 31907583 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Thiazolidines
• lipopolysaccharide, E coli O55-B5
• 2-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4-carboxylic acid
• Cysteine

Topics

• Animals
• Antioxidants (pharmacology)
• Behavior, Animal (drug effects)
• Brain (drug effects, metabolism, physiopathology)
• Cysteine (analogs & derivatives, pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation Mediators (metabolism)
• Lipopolysaccharides
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Memory Disorders (chemically induced, metabolism, prevention & control, psychology)
• Mice
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Recognition, Psychology (drug effects)
• Signal Transduction
• Social Behavior
• Thiazolidines (pharmacology)