title: Doxycycline suppression of ischemia-reperfusion-induced hepatic injury.
abstract: Leukocytes, in particular polymorphonuclear neutrophils (PMNs), are believed to play a central role in ischemia-reperfusion (I/R)-induced tissue injury. Changes in endothelial cells occurring during ischemia promote PMN binding to these cells during reperfusion, which primers PMN synthesis of oxygen radicals and release of cytotoxic proteins. These events lead to vascular damage and subsequent tissue injury. Recently we have shown that doxycycline (Dc), a member of the tetracycline family of antibiotics, inhibits PMN superoxide (O2) synthesis and degranulation in vitro. It also suppresses PMN-mediated RBC, fibroblast, and endothelial cytotoxicity, properties of the drug that may make it of use to protect tissues from I/R-induced injury. In this study we demonstrate that Dc administration either prior to clamping of the portal circulation, or 1 h after the reperfusion, significantly suppressed liver damage as assessed by serum levels of a marker of hepatic injury, alanine aminotransferase (s-ALT). The reduction in s-ALT was not a result of reduced reflow in the Dc-treated rats as indicated by Evans' blue perfusion data. The findings suggest that Dc and possibly other tetracyclines may be of value in protecting tissues and organs from I/R-mediated damage even if the drug is given after the ischemic event has occurred.
authors.affiliation: Department of Biologic Structure and Function and Oral Molecular Biology School of Dentistry, Oregon Health Sciences University, Portland 97201.
authors.forename: J R
authors.initials: JR
authors.lastname: Smith
authors.forename: W L
authors.initials: WL
authors.lastname: Gabler
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004318:Doxycycline / Q000494:pharmacology*; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D013997:Time Factors
chemical_list: D000410:Alanine Transaminase; D004318:Doxycycline