Role of Stem Cells and Antioxidant on Modulation of Body Defense Mechanism in Lipopolysaccharide- Induced Acute Lung Injury in Rats
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- Category: Vol. 80, September 2012
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Role of Stem Cells and Antioxidant on Modulation of Body Defense Mechanism in Lipopolysaccharide- Induced Acute Lung Injury in Rats,SAMAH EL-ATTAR, LAILA A. ELSAYED and LAILA RASHED
Abstract
Background: Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. Current treatment remains primarily supportive with lung-protective ventilation and a fluid conservative strategy. Despite improvements in critical care and mechanical ventilation protocols, the mortality rate for patients with ALI is still 30% to 40%.
Aim of Work: This study was designed to investigate the effect of stem cells and antioxidant treatment on lipopolysac-charide (LPS)-induced acute lung injury in rats, and to explore possible underlying mechanisms.
Methods: Thirty male adult albino rats were randomly divided into 5 experimental groups:
Group 1: Normal rats injected with vehicle solution phosphate buffered saline (PBS)
Group 2: LPS group, the rats were injected with 10mg/kg of LPS in sterile PBS i.p.
Group 3: LPS + N-acetylcysteine (NAC), the rats were injected i.p. with 10mg/kg of LPS and treated with NAC 4.8g/l of drinking water 2 days before LPS injection and maintained until the day of study.
Group 4: LPS + Mesenchymal stem cells (MSCs), the rats of this group were injected i.p. with 10mg/kg of LPS and 3 hours later were given 5X105 BMDMSC in 0.1mL PBS.
Group 5: LPS+NAC+MSCs, rats of this group were injected i.p. with 10mg/kg of LPS and after 3hours, the rats were given 5X105 bone marrow derived mesenchymal cells (BMDMSC) in 0.1mL PBS and NAC 4.8g/l of drinking water for 2 days before the LPS procedure and was main-tained until the day of study. 24 hours after LPS injection, broncho-alveolar lavage fluid (BALF) was obtained, analyzed for protein, cellular content and% of neutrophils. Lungs were excised for determination of their water content, inflammatory markers, apoptosis and growth factors.
Results: Our results showed that lung injury parameters, including the wet/dry weight ratio and protein, cellular content and percent of neutrophils in BALF, were significantly higher in the LPS group than in the PBS group (p<0.05). In the LPS group, significant higher MDA level, NF-icB, IL10, and fas1expression and MPO (myloperoxidase) activity in lung homogenates were observed when compared with the PBS group (p<0.05). There was a marked decrease in kertinocytes growth factor (KGF) expression in lung tissues in response to LPS challenge (p<0.05, LPS group vs PBS group). Stem cells and NAC pretreatment, significantly attenuated LPS-induced inflammation, oxidative stress and apoptosis in treated rats. Stem cells and NAC significantly increased KGF and IL10 expression. Either stem cell therapy or NAC treatment improved epithelial barrier function with significant decrease in protein, cellular content and percent neutrophil in BAL compared with LPS group. Combined therapies induced a significantly greater improvement as compared to each therapy alone.
Conclusion: Stem cells and NAC pretreatment attenuates LPS-induced lung injury in rats. This beneficial effects may involves, inhibition of neutrophilic recruitment, inflammation, oxidative stress, apoptosis, and possibly through activation of lung expression of kertinocytes growth factor.