Details

Autor(en) / Beteiligte

• Fiorini, Ryan N.
• Shafizadeh, Stephen F.
• Polito, Carmen
• Rodwell, David W.
• Cheng, Gang
• Evans, Zachary
• Wan, Chidan
• Belden, Sarah
• Haines, Julia K.
• Birsner, Jennifer
• Lewin, David
• Wasiluk, Karen R.
• Dunn, David L.
• Schmidt, Michael G.
• Chavin, Kenneth D.

Titel

Anti‐Endotoxin Monoclonal Antibodies are Protective against Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

Ist Teil von

• American journal of transplantation, 2004-10, Vol.4 (10), p.1567-1573

Ort / Verlag

9600 Garsington Road , Oxford , OX4 2DQ , UK: Munksgaard International Publishers

Erscheinungsjahr

2004

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti‐LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta‐hepatis occlusion and varying lengths of reperfusion with or without pre‐treatment with an anti‐LPS mAb. There was 14–31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75–83% of ob/ob mice pre‐treated with an anti‐LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti‐LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti‐LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.