Montelukast Attenuates Abdominal Aortic Aneurysm in Rats: Anti-Inflammatory and Antioxidant Effects

Abstract

Objective: Oxidative stress and inflammation are widely recognized as central mechanisms in the pathogenesis of abdominal aortic aneurysm. This study sought to examine the potential protective properties of montelukast in a rat model of aortic aneurysm. Methods: Male Sprague-Dawley rats were randomly allocated into three experimental groups. Abdominal aortic aneurysm was induced using the calcium chloride (CaCl2) model, in which gauze soaked in 0.5 M CaCl2 was placed directly onto the adventitial surface of the infrarenal abdominal aorta for 15 minutes. After induction, the treatment group received daily intraperitoneal injections of montelukast (10 mg/kg) for 4 consecutive weeks. At the study end point, animals were euthanized, and infrarenal aortic tissues were harvested for biochemical and histological evaluations. Measured parameters included matrix metalloproteinase (MMP)-2 and MMP-9 expression, myeloperoxidase (MPO) activity, and 8-hydroxy-2 '-deoxyguanosine levels. Antioxidant capacity was assessed through superoxide dismutase (SOD) activity assays. Histopathological examinations were performed, and statistical analysis was conducted using GraphPad Prism v.5. Results: Exposure to CaCl2 triggered pronounced oxidative injury and inflammation, as evidenced by elevated 8-hydroxy-2 '-deoxyguanosine levels, increased MPO activity, reduced SOD activity, and upregulated MMP-2 and MMP-9 expression. Montelukast administration markedly attenuated these changes, normalizing oxidative and inflammatory markers while improving histopathological architecture. Conclusions: Montelukast effectively counteracted CaCl2-induced aortic damage. The protective effects of montelukast appear to be mediated through suppression of MMP activity, restoration of SOD levels, and reduction of MPO-driven oxidative injury. By mitigating both inflammatory and oxidative mechanisms, montelukast contributes to the preservation of aortic wall structure. Clinical Relevance: Abdominal aortic aneurysm remains a major vascular disorder without an effective pharmacological therapy to slow its progression. In this experimental study, montelukast, a leukotriene receptor antagonist widely used in asthma, attenuated abdominal aortic aneurysm formation in rats and was associated with increased superoxide dismutase activity, reduced myeloperoxidase levels, and suppressed matrix metalloproteinase activation. These combined antioxidant, anti-inflammatory, and matrix-stabilizing effects preserved aortic wall integrity. Given montelukast's established safety and clinical availability, these findings support its potential for future clinical investigation as a pharmacological approach to limit aneurysm progression. (JVS-Vascular Science 2026;7:100405.)