Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Sepsis caused by lipopolysaccharide (LPS) is a life-threatening disease accompanied by multiple organ failure. This study investigated the curative effects of N-acetylcysteine (NAC), bone marrow derived mesenchymal stem cells (BM-MSCs), or imatinib (IMA) against hepatic, renal and pulmonary responses caused by single administration of LPS (10 mg/kg, i.p) in rats. Treatment with BM-MSCs (5{u00D7}105 in 0.1 ml PBS, i.p.) 3 hours after LPS, or IMA (15 mg/kg, i.p.) 30 minutes after LPS antagonized the LPS-induced elevation of the liver enzymes (ALT, AST), kidney functions (BUN, sCr) as well as the increased lung pulmonary vascular permeability and pulmonary edema. Both BM-MSCs and IMA decreased tissues{u2019} contents of the TNF-Ü, NF-mB, IL-1Ý, iNOS, P38-MAPK, STAT-3, Bax. They also increased the anti-inflammatory cytokine IL-10 and the anti-apoptotic mediator Bcl-2. Meanwhile, rats exhibited marked reduction of the broncho-alveolar lavage fluid contents of TNF-Ü, IL-1Ý, IFN-Þ, and neutrophils count. These ameliorative effects were comparable to those produced by NAC (300 mg/kg, p.o) given once directly after LPS. Notably, BM-MSCs exerted anti-inflammatory, anti-oxidant as well as anti-apoptotic potentials to a better extent than IMA. In conclusion, BM-MSCs and IMA can be probably introduced as candidates for the treatment of systemic inflammation caused by LPS.

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