Abstract
The activation of the Nrf2/HO-1 signaling pathway regulates cellular antioxidant stress and exerts anti-inflammatory and cytoprotective effects against acute lung injury (ALI). The present study aimed to evaluate the therapeutic role of L-carnitine (LC) against potassium dichromate (PD) - induced acute lung injury in adult male albino rats via modulation of Nrf2/HO-1 signaling pathway. For this purpose, forty rats were randomly allocated into 5 groups (8 rats each). The normal group received intranasal (i.n.) saline, while the ALI group received intranasal instillation of PD as a single dose of 2 mg/kg. The 3d – 5th groups received PD then after 24 h administered L-carnitine (25, 50 and 100 mg/kg; orally) for 3 consecutive days. The therapeutic effect of L-carnitine was evaluated by assessment of serum levels of glutathione (GSH) and malondialdehyde (MDA) along with measurement of lung contents of transforming growth factor β1 (TGFβ1), protein kinase B (AKT), Nuclear factor erythroid-2 related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 enzyme (NQO1) and glutathione cysteine ligase modifier subunit (GCLM) expression. Post-treatment with L-carnitine effectively increased the levels of GSH and AKT, elevated Nrf2 and its target genes and decreased the levels of MDA and TGFβ1 in comparison with PD control rats. Additionally, L-carnitine effectively reduced the number of goblet cell, inhibited the mucus formation in bronchioles and interstitial inflammatory infiltrate as well as alleviated the destruction of alveolar walls, and the congestion of blood vessels in lung tissue induced by PD. Our findings showed that L-carnitine may be a promising therapeutic agent against PD-induced acute lung injury.
Highlights
Acute lung injury (ALI) or its extreme manifestation, acute respiratory distress syndrome (ARDS), is an acute inflammatory lung injury which associated with high morbidity and mortality along with the progression of multiple organ failure [1]
We aimed to explore the possible therapeutic role of L-carnitine against potassium dichromate (PD) induced acute lung injury via modulation of Nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway
Treatment with L-carnitine 100 mg/kg returned tissue Kelch-like ECH-associated protein 1 (Keap1) to its normal values (Figure 2a, b)
Summary
Acute lung injury (ALI) or its extreme manifestation, acute respiratory distress syndrome (ARDS), is an acute inflammatory lung injury which associated with high morbidity and mortality along with the progression of multiple organ failure [1]. The main pathological features of ALI include diffuse alveolar epithelial damage, pulmonary vascular endothelial cells, neutrophils infiltration and influx of protein-rich fluid into the alveolar spaces [3, 4]. The potential mechanisms of ALI may include inflammatory reactions, apoptosis, redox imbalance [5] and goblet cell hyperplasia (GCH) [6]. Cr VI can generate reactive oxygen species (ROS) during their reduction, and these ROS can cause injury to the cellular proteins, lipids, and DNA [9]. An imbalance between generation and removal of ROS via antioxidant defense system can lead to oxidative stress [11]
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