Department of Pharmacology and Therapeutics, Neuropharmacology Unit, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Department of Pharmacology, Faculty of Basic Medical Sciences, PAMO University of Medical Sciences, River States, Port Harcourt, Nigeria.
Naunyn Schmiedebergs Arch Pharmacol. 2020 May;393(5):909-925. doi: 10.1007/s00210-019-01805-0. Epub 2020 Jan 7.
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.
D-核糖-L-半胱氨酸（DRLC）是半胱氨酸的类似物，可提高谷胱甘肽（GSH）的含量，已被报道可减轻氧化应激介导的疾病。本研究旨在评估 DRLC 对记忆缺陷以及脂多糖（LPS）诱导的小鼠生化和组织形态变化的影响。雄性瑞士小鼠（n=10）用三种剂量的 DRLC（25mg/kg、50mg/kg 和 100mg/kg）、多奈哌齐（1mg/kg）或载体（生理盐水）预处理 30min，然后每天腹膜内注射 LPS（0.25mg/kg），共 7 天。使用 Y 迷宫、物体识别和社交识别测试评估记忆功能。评估特定脑区（前额叶皮层和海马体）以确定氧化应激生物标志物（丙二醛、GSH 和过氧化氢酶）、乙酰胆碱酯酶活性、促炎细胞因子（肿瘤坏死因子-α和白细胞介素-6）、核因子-κB（NF-κB）的表达和神经元细胞形态。DRLC（25-100mg/kg）逆转了 LPS 处理小鼠的记忆缺陷（p<0.05）。DRLC 显著降低了 LPS 处理小鼠脑区中氧化应激和促炎细胞因子的增加（p<0.05）。DRLC（50mg/kg 和 100mg/kg）还降低了 LPS 处理小鼠大脑中的乙酰胆碱酯酶活性并降低了 NF-κB 的表达。最后，它减轻了 LPS 诱导的小鼠前额叶皮层和海马体的细胞结构扭曲和神经元细胞丢失。这项研究的结果表明，DRLC 通过抑制氧化应激、释放促炎细胞因子和表达 NF-κB 来减轻 LPS 诱导的小鼠记忆缺陷。
