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.
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 [...]