Abstract
OBJECTIVES: Effect of alpha-linolenic acid (ALA) against ovalbumin (OVA)-induced inflammation, oxidant/antioxidant imbalance and pathological features was examined in rat. METHODS: Total and differential WBC count and oxidant/antioxidant levels in BALF (bronchoalveolar lavage fluid) as well as lung pathological features were investigated in five groups of rats including controls (group C), rats sensitized with OVA (group S) and S treated with either ALA (0.2 and 0.4 mg/ml) or dexamethasone. KEY FINDINGS: As compared to group C, in OVA-sensitized rats, increases in WBC counts, levels of oxidant biomarkers and most pathological scores were observed while lymphocyte percentage and antioxidants levels decreased. Treatment with ALA (0.2 and 0.4 mg/ml) significantly reduced total WBC, NO2 and NO3 levels, interstitial fibrosis and emphysema compared to sensitized group. The higher dose of ALA also significantly decreased neutrophil, eosinophil, and monocyte counts, MDA levels and interstitial inflammation but increased lymphocyte counts, as well as antioxidants levels, compared to sensitized group. Dexamethasone administration led to a significant improvement of most factors compared to group S but had no effects on total WBC count, bleeding and epithelial damage. CONCLUSIONS: Alpha-linolenic acid suppressed inflammation and oxidative stress, making it a potential therapeutic candidate for treatment of airway inflammatory diseases such as bronchial asthma.
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Key Points
Asthma as a chronic condition is regarded as a major health issue worldwide. This disease is described by pulmonary eosinophilia, lymphocyte and neutrophil infiltration, mucus hypersecretion and airway hyperresponsiveness (AHR). Increased oxidative stress (OS) is a major player in chronic airway inflammation observed in asthma. Overproduction of reactive oxygen (ROS) and enhanced levels of OS biomarkers were observed in asthma. Alpha-linolenic acid has been used for human growth and development and prevention of diseases. Several therapeutic activities such as antioxidant, anti-inflammatory, anticonvulsant and relaxant effects have been shown for ALA. In this study, the effects of ALA on lung pathological features, total and differential WBC counts, as well as OS biomarkers in BALF (bronchoalveolar lavage fluid) of OVA-sensitized rats as an animal model of bronchial asthma, were investigated. The results showed in BALF obtained from OVA-sensitized rats, lymphocyte percentage was reduced which was probably due to increased total WBC count. Results indicated marked increases in levels of NO2 and NO3 (as NO oxidation products) and MDA (as a lipid peroxidation marker) while the levels of SOD, CAT and thiol as antioxidant enzymes decreased in OVA-sensitized rats which also confirmed the induction of sensitization. Based on this data, ALA significantly reduced total WBC count, neutrophils, eosinophils and monocytes percentages, NO2, NO3 and MDA levels, and pathological insults (in terms of interstitial inflammation and fibrosis, emphysema, and epithelial damage) but increased lymphocyte percentages as well as SOD, thiol and CAT levels compared to the sensitized group. These findings indicate preventive effects of ALA on inflammatory cells, oxidant–antioxidant markers and pathological damages in OVA-sensitized animals. The results of the current study indicate that ALA ameliorates oxidative stress and lung inflammation in OVA-sensitized rats, supporting the asthma-preventive potential of ALA. Together, these data indicated an asthma-preventive potential for ALA which is mediated through ALA effects on lung inflammatory cells, oxidative markers and lung pathological damages in sensitized rats. These effects were comparable to the effect of dexamethasone at used concentrations.