L-carnitine alleviated acute lung injuries induced by potassium dichromate in rats: involvement of Nrf2/HO-1 signaling pathway

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.

Budesonide-Loaded Bilosomes as a Targeted Delivery Therapeutic Approach Against Acute Lung Injury in Rats

“…Thus, inclusion of BUD within bilosomes could boost its therapeutic activity. TNF-α and TGF-β1 stimulation have an important role in acute lung injury via inducing inflammation and releasing ROS which in turn affect bronchioles that become filled by mucous and destruct alveolar walls 19 . Previous studies revealed that BUD decreased TNF-α in Wistar male rats with injured lungs 88 .…”

“…Potassium dichromate (PD) contains chromium (Cr) which can induce acute lung injury (ALI) and is accompanied by high morbidity and mortality 19 . Cr is widely used in industries released toxic compounds such as hexavalent form (chromium VI) causing carcinogenic, mutagenic, teratogenic effects 20 , 21 and multiple organ failure such as lung 19 and kidney via inflammatory cytokine NF-κβ 22 . Also in lung, Cr generates reactive oxygen species (ROS) and inflammatory cytokine TGF-β inducing acute lung injury.…”

Microscopic Vision for a Therapeutic Effect of Carnitine and Arginine Against Cadmium Toxicity in the Histological Structure of Rat Lung

“…A study performed by Salama et.al. 4 mentions that giving oral doses of L-carnitine at a concentration of 25 mg/kg to white male rats treated with chromium at a concentration of 2 mg/kg has a therapeutic effect in acute lung injury caused by chromium in acting as an antioxidant and anti-inflammatory mediated by the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways.…”

“…Therefore, antioxidants such as carnitine and arginine may have an active role in protecting cellular components from oxidants. 4,5…”

Novel Neuroprotective Potential of Bunchosia armeniaca (Cav.) DC against Lipopolysaccharide Induced Alzheimer’s Disease in Mice

“…The wells were filled with tetramethylbenzidine (TMB) substrate solution and kept for 15 min of incubation at 37 °C; a color was produced in proportion to the quantity of NF-κB, IL-1β, CYP2E1, and GFAP bound. A stop solution was added to the wells to terminate the color development, and color intensity was detected at 450 nm after 10 min [ 130 ].…”