Montelukast reduces sepsis-induced lung and renal injury in rats

Abstract

This study was undertaken to examine the effects of montelukast (MNT) on lung and kidney injury in lipopolysaccharide (LPS) induced systemic inflammatory response. Rats were randomized into 5 groups (n = 8 rats/group): (i) Control; (ii) LPS treated (10 mg/kg body mass, by intraperitoneal (i.p.) injection); (iii) LPS + MNT (10 mg/kg, per oral (p.o.)); (iv) LPS + MNT (20 mg/kg, p.o); (v) LPS + dexamethasone (DEX; 1 mg/kg, i.p.). Twenty-four hours after sepsis was induced, the lung or kidney:body mass ratio and percent survival of rats were determined. Creatinine, blood urea nitrogen (BUN), albumin, total protein, and LDH activity were measured. Lung and kidney samples were taken for histological assessment and for determination of their malondialdehyde (MDA) and glutathione (GSH) contents. The expression of tumour necrosis factor α (TNF-α) in tissue was evaluated immunohistochemically. LPS significantly increased the organ:body mass ratio, serum creatinine, BUN, and LDH, and decreased serum albumin and total protein levels. MDA levels increased in lung and kidney tissues after treatment with LPS, and there was a concomitant reduction in GSH levels. Immunohistochemical staining of lung and kidney specimens from LPS-treated rats revealed high expression levels of TNF-α. MNT suppresses the release of inflammatory and oxidative stress markers. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. These results demonstrate that MNT could have lung and renoprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and (or) anti-inflammatory properties.

A Novel Strategy to Mitigate the Hyperinflammatory Response to COVID-19 by Targeting Leukotrienes

“…The rationale for the role of leukotrienes in COVID-19 pathogenesis is clear. A wealth of information exists on elevated LTs in ARDS/sepsis/end organ failure in humans and efficacy of both zileuton and montelukast in various preclinical models (Sprague et al, 1989;Davis et al, 1990;Bernard et al, 1991;Westcott et al, 1991;Collin et al, 2004;Khodir et al, 2014;Monteiro et al, 2014). The roles of LTs in COVID-19 have been neglected to date.…”

Metabolomic analysis for the protective effects of mangiferin on sepsis‐induced lung injury in mice

“…Glutathione, which is one of the major components of the nonenzymatic antioxidant system provides cellular protection against damage from oxygen‐derived free radicals (Newsholme et al, ). Glutathione acts as a substrate for the glutathione peroxidase‐mediated reduction reaction of H 2 O 2 into nontoxic products such as H 2 O and blocks lipid peroxidation (Khodir, Ghoneim, Rahim, & Suddek, ). For reasons outlined above, the expression level of glutamine implied that MF might have an impact on the glutamine and glutamate metabolic pathways.…”

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

“…Finally, LC antioxidant power may be due to its ability to increase activities of antioxidant enzymes like SOD and others 7,8,25 . Regarding ML, it was reported to correct lipopolysaccharide (LPS)-induced elevations in TBARS and depletion in GSH in a lung model of injury 26 . On the other side, investigation of anti-inflammatory potential of ML and LC in the current investigation revealed true anti-inflammatory ability of both agents represented by significant reductions of COX-II and LOX levels in sera of ML or LC-pretreated rats compared with control CP rats ( Table 2).…”