左旋肉碱通过一氧化氮通路对抗氯喹引起的瘙痒的止痒作用。
Anti-pruritic effect of L-carnitine against chloroquine-induced pruritus mediated via nitric oxide pathway.
机构信息
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Department of Biomedical Science, Pak-Austria Fachhochule: Institute of Applied Science and Technology, Mang Haripur, KPK, Pakistan.
出版信息
BMC Pharmacol Toxicol. 2024 May 22;25(1):32. doi: 10.1186/s40360-024-00748-4.
BACKGROUND
Pruritus, or itching, is a distressing symptom associated with various dermatological and systemic diseases. L-carnitine (βeta hydroxy-γ-tri methyl amino-butyric acid), is a naturally occurring substance, it controls numerous physiological processes. The present research aims to identify L-carnitine for its anti-pruritic effect via nitric oxide-dependent mechanism.
METHODS
Chloroquine-induced pruritus serves as an experimental model to investigate possible therapeutic interventions. In this study, we evaluated the efficacy of L-carnitine in combating oxidative stress, nitric oxide, and inflammatory cytokines in a chloroquine-induced pruritus model.
RESULTS
L-carnitine treatment significantly reduced scratching behavior compared to the disease group (P < 0.001 vs. chloroquine group), indicating its antipruritic potential. The markers of oxidative stress, GST, GSH, Catalase, and LPO were dysregulated in the disease model, but administration of L-carnitine restored GST, GSH, and Catalase levels and decreased LPO levels (P < 0.001 vs. chloroquine group), thereby alleviating oxidative stress. L-carnitine also reduced nitric oxide synthase (NOS) activity, suggesting that it modulates nitric oxide signaling pathways involved in pruritus. In addition, L-carnitine lowered levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), inflammatory marker nuclear factor kappa B (p-NFκB) and also reduces an inflammatory enzyme, cyclooxygenase-2 (COX-2), determined by ELISA (Enzyme-Linked Immunosorbent Assay) (P < 0.001 vs. chloroquine group). It downregulates nNOS mRNA expression confirmed by real-time polymerase chain reaction (RT-PCR).
CONCLUSION
These findings highlight the therapeutic effects of L-carnitine in alleviating chloroquine-induced pruritus.
背景
瘙痒，或刺痒，是与各种皮肤和系统疾病相关的一种痛苦症状。左旋肉碱（β-羟基-γ-三甲氨基丁酸）是一种天然存在的物质，它控制着许多生理过程。本研究旨在通过一氧化氮依赖的机制确定左旋肉碱的抗瘙痒作用。
方法
氯喹诱导的瘙痒作为一种实验模型，以研究可能的治疗干预措施。在这项研究中，我们评估了左旋肉碱在对抗氯喹诱导的瘙痒模型中的氧化应激、一氧化氮和炎症细胞因子中的疗效。
结果
与疾病组相比，左旋肉碱治疗显著减少了搔抓行为（P<0.001 与氯喹组相比），表明其具有抗瘙痒潜力。疾病模型中 GST、GSH、Catalase 和 LPO 的氧化应激标志物失调，但左旋肉碱的给药恢复了 GST、GSH 和 Catalase 水平并降低了 LPO 水平（P<0.001 与氯喹组相比），从而减轻了氧化应激。左旋肉碱还降低了一氧化氮合酶（NOS）的活性，表明它调节了参与瘙痒的一氧化氮信号通路。此外，左旋肉碱降低了促炎细胞因子如肿瘤坏死因子-α（TNF-α）、炎症标志物核因子 kappa B（p-NFκB）的水平，并通过酶联免疫吸附试验（ELISA）降低了炎症酶环氧化酶-2（COX-2）的水平（P<0.001 与氯喹组相比）。实时聚合酶链反应（RT-PCR）证实其下调了 nNOS mRNA 表达。
结论
这些发现强调了左旋肉碱在缓解氯喹诱导的瘙痒中的治疗作用。
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