caa a22 4500 445853395 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00204-011-0663-8 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0663-8 Silencing of tissue factor by antisense deoxyoligonucleotide prevents monocrotaline/LPS renal injury in mice [Elektronische Daten] [Mohamed Abdel-Bakky, Mohamed Hammad, Larry Walker, Mohammad Ashfaq] Tissue factor (TF) is involved in monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity. It is not known whether MCT/LPS can cause renal toxicity and whether TF is involved in this toxicity. Thus, the present study was undertaken to investigate the potential renal toxicity after MCT/LPS co-treatment and the involvement of TF in this toxicity. MCT was delivered to ND4 male mice (200mg/kg) per os followed 4h later by treatment with LPS ip (6mg/kg) to investigate its effect on kidney. We injected TF antisense oligonucleotide (TF-AS) intravenously (i.v) in mice prior to LPS treatment, to block TF, and measured their blood urea nitrogen (BUN), creatinine (CRE), alkaline phosphatase (ALP), and potassium. In MCT/LPS co-treated group, fibrin was detected on the glomerular capillary lumina, distal tubules of renal cortex, and the necrotic tubules of renal medulla. An elevation of BUN, creatinine, and the BUN/creatinine ratio was seen in mice with MCT/LPS co-treatment, compared to animals receiving LPS or MCT alone. Simultaneously, an aggressive tubular necrosis was seen in the medullary tubules in the same group which may account for the oliguria observed in these animals. Fourfold inductions in the plasma TF level was detected at 10h after MCT/LPS co-treatment which increased to 18-fold at 24h. Increased blood level of leptin, interleukin-6 (IL-6) and downregulation of tubular chemokine (C-X-C motif) ligand 16 (CXCL16) are characteristic features in MCT/LPS co-treated animal. On the other hand, mice injected with TF-AS in the presence of MCT/LPS co-treatment showed no elevation of the blood BUN, creatinine, potassium, and normal levels of the proinflammatory molecules. TF-AS injection significantly prevented glomerular and tubular fibrin deposition, tubular necrosis, and improvement of the animal survivability. Renal toxicity involving TF can be prevented successfully by the use of TF-AS. Springer-Verlag, 2011 Tissue factor antisense nationallicence Monocrotaline nationallicence Lipopolysaccharide nationallicence Renal toxicity nationallicence Abdel-Bakky Mohamed National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Hammad Mohamed National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Walker Larry National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Ashfaq Mohammad National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1245-1256 0340-5761 85:10<1245 2011 85 204 https://doi.org/10.1007/s00204-011-0663-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0663-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Abdel-Bakky Mohamed National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 700 1- Hammad Mohamed National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 700 1- Walker Larry National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 700 1- Ashfaq Mohammad National Center For Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/10(2011-10-01), 1245-1256 0340-5761 85:10<1245 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer