Chloroquine Protects Against Mesenteric Ischemia: Insights Into the Role of Nitrergic and Opioidergic Systems Publisher Pubmed



Emami SAM ; Mohammadihamaneh A ; Ghasemi M ; Abdollahi A ; Jouyban K ; Mohammad Jafari R ; Abdolghaffari AH ; Dehpour AR
Source: Inflammopharmacology Published:2025

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. © 2025 Elsevier B.V., All rights reserved.