Chloroquine protects against mesenteric ischemia: insights into the role of nitrergic and opioidergic systems.

IF 5.3 2区 医学 Q2 IMMUNOLOGY
Seyed Amir Mahdi Emami, Amirabbas Mohammadi Hamaneh, Moein Ghasemi, Alireza Abdollahi, Kimiya Jouyban, Razieh Mohammad Jafari, Amir Hossein Abdolghaffari, Ahmad Reza Dehpour
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引用次数: 0

Abstract

Background: Acute mesenteric ischemia is a severe condition with high mortality and no established pharmacological treatment, driven by oxidative stress, inflammation, and microvascular dysfunction. Chloroquine, an immunomodulatory agent, has shown protective effects in ischemic models, but its role in mesenteric ischemia and its interaction with regulatory pathways remain unclear.

Objective: To evaluate protective effects of chloroquine in mesenteric ischemia and its interaction with the nitrergic and opioidergic systems.

Methods: Eighty-four male Wistar rats were randomly assigned to fourteen groups and subjected to sixty minutes of mesenteric artery occlusion, followed by sixty minutes of reperfusion. Chloroquine (1-10 mg/kg) was administered, with the minimal effective dose (5 mg/kg) combined with a nitric oxide synthase inhibitor, a nitric oxide precursor, or an opioid receptor antagonist or agonist. Histopathological assessments and biochemical analyses of oxidative and inflammatory markers were conducted.

Results: Chloroquine at 5 and 10 mg/kg significantly reduced histopathological scores, with the 5 mg/kg dose associated with increased glutathione and reduced malondialdehyde, myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and nuclear factor kappa B levels. The opioidergic system contributed to antioxidant effects, enhancing reductions in malondialdehyde and nitric oxide levels, while increasing glutathione levels. In contrast, its anti-inflammatory properties were influenced by the nitrergic pathway, as indicated by increased nuclear factor kappa B levels and histopathological scores upon N(ω)-nitro-L-arginine methyl administration.

Conclusion: Chloroquine protects against mesenteric ischemia by modulating oxidative and inflammatory pathways, with the opioidergic and nitrergic systems mediating its effects. These findings highlight a potential therapeutic role for chloroquine, warranting further investigation.

氯喹对肠系膜缺血的保护作用:氮能和阿片能系统的作用。
背景:急性肠系膜缺血是一种由氧化应激、炎症和微血管功能障碍驱动的严重疾病,死亡率高,没有成熟的药物治疗方法。氯喹是一种免疫调节剂,在缺血模型中显示出保护作用,但其在肠系膜缺血中的作用及其与调节途径的相互作用尚不清楚。目的:探讨氯喹对肠系膜缺血的保护作用及其与氮能系统和阿片能系统的相互作用。方法:84只雄性Wistar大鼠随机分为14组,经肠系膜动脉阻断60分钟后再灌注60分钟。给予氯喹(1- 10mg /kg),最小有效剂量(5mg /kg)与一氧化氮合酶抑制剂、一氧化氮前体或阿片受体拮抗剂或激动剂联合使用。进行组织病理学评估及氧化和炎症标志物的生化分析。结果:5和10 mg/kg剂量的氯喹显著降低组织病理学评分,5 mg/kg剂量与谷胱甘肽升高和丙二醛、髓过氧化物酶、肿瘤坏死因子- α、白细胞介素-6和核因子κ B水平降低相关。阿片能系统有助于抗氧化作用,增强丙二醛和一氧化氮水平的降低,同时增加谷胱甘肽水平。相反,N(ω)-硝基- l -精氨酸甲基给药后,核因子κ B水平和组织病理学评分升高,表明其抗炎特性受到氮能途径的影响。结论:氯喹通过调节氧化和炎症通路,通过阿片能和氮能系统介导其对肠系膜缺血的保护作用。这些发现强调了氯喹的潜在治疗作用,值得进一步研究。
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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
期刊介绍: Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]
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