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Anti‐Endotoxin Monoclonal Antibodies are Protective against Hepatic Ischemia/Reperfusion Injury in Steatotic Mice
Author(s) -
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.
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00549.x
Subject(s) - medicine , monoclonal antibody , reperfusion injury , ischemia , pharmacology , antibody , immunology
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.