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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

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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.

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Acknowledgments

We thank the technical staff of the Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan for their kind assistance. We would also like to acknowledge Michael O. S. Afolabi, PhD, Postdoctoral Fellow, Department of Pediatrics and Child Health, University of Manitoba, Canada, for his editorial assistance with the manuscript.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Osagie Emokpae, Benneth Ben-Azu, Abayomi M. Ajayi & Solomon Umukoro

  2. Department of Pharmacology, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, River States, Port Harcourt, Nigeria

    Benneth Ben-Azu

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  1. Osagie Emokpae
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  2. Benneth Ben-Azu
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OE, BB, and SU conceived and designed the study. OE, BB, and AMA conducted experiments. OE and BB analyzed data. BB and SU wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Solomon Umukoro.

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Emokpae, O., Ben-Azu, B., Ajayi, A.M. et al. 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. Naunyn-Schmiedeberg's Arch Pharmacol 393, 909–925 (2020). https://doi.org/10.1007/s00210-019-01805-0

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