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Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats.

ABSTRACT: This research was conducted to investigate possible protective influences of levocetirizine, a nonsedating H1 antihistamine, against lipopolysaccharide (LPS)-induced lung injury in rats. Male Sprague Dawley rats received either levocetirizine (1?mg/kg/day, orally) or the vehicle of the drug (2?ml/kg/day, orally) for 1 week before a single IP injection of LPS (7.5?mg/kg). A group of normal rats served as control. The experiments were terminated 18?h after the LPS challenge. Serum C-reactive protein levels were determined. Moreover, total cell count, lactate dehydrogenase (LDH) activity, protein levels, and total NOx were evaluated in bronchoalveolar lavage fluid (BALF). Pulmonary edema was evaluated as the wet/dry lung weight ratio. Lung tissue homogenate was assessed for antioxidant/pro-oxidant status. BALF and lung tissue levels of tumor necrosis factor-? (TNF-?) were assessed. Lungs were examined for histological alterations. LPS-mediated lung injury was manifested by pulmonary edema, leukocyte infiltration, oxidative stress, and inflammation. Levocetirizine attenuated lung edema and mitigated the increases in BALF protein levels, LDH activity, and lung leukocyte recruitment in LPS-challenged rats. Additionally, TNF-? protein levels in BALF and lung tissue were diminished by levocetirizine administration. Levocetirizine also exhibited a potent antioxidant activity as indicated by a decrease in lung tissue levels of malondialdehyde and an enhancement of superoxide dismutase activity. Histological examination of lung tissues confirmed the beneficial effect of levocetirizine against LPS-induced histopathological alterations. In conclusion, levocetirizine may offer protection against lung tissue damage and inflammation in LPS-challenged rats.

SUBMITTER: Fahmi ANA

PROVIDER: S-EPMC6110004 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats.

Fahmi Alaa N A ANA Shehatou George S G GSG Salem Hatem A HA

BioMed research international 20180813

This research was conducted to investigate possible protective influences of levocetirizine, a nonsedating H<sub>1</sub> antihistamine, against lipopolysaccharide (LPS)-induced lung injury in rats. Male Sprague Dawley rats received either levocetirizine (1 mg/kg/day, orally) or the vehicle of the drug (2 ml/kg/day, orally) for 1 week before a single IP injection of LPS (7.5 mg/kg). A group of normal rats served as control. The experiments were terminated 18 h after the LPS challenge. Serum C-rea ...[more]

PMID: 30186866

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Project description:BackgroundAcute respiratory distress syndrome (ARDS) is a severe and life-threatening acute lung injury (ALI) that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK) pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred)-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK)-MAPK pathway, in lipopolysaccharide (LPS)-induced acute lung inflammation.MethodsWild-type (WT) mice and Spred-2(-/-) mice were exposed to intratracheal LPS (50 µg in 50 µL PBS) to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2(-/-) mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells.ResultsLPS-induced acute lung inflammation was significantly exacerbated in Spred-2(-/-) mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-?, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2(-/-) mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells.ConclusionsThe ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls the development of LPS-induced lung inflammation by negatively regulating the ERK-MAPK pathway. Thus, Spred-2 may represent a therapeutic target for the treatment of ALI.

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Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats.

Publications

Levocetirizine Pretreatment Mitigates Lipopolysaccharide-Induced Lung Inflammation in Rats.

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