Minocycline decreases liver injury after hemorrhagic shock and resuscitation in mice

Patients that survive hemorrhage and resuscitation (H/R) may develop a systemic inflammatory response syndrome (SIRS) that leads to dysfunction of vital organs (multiple organ dysfunction syndrome, MODS). SIRS and MODS m
Patients that survive hemorrhage and resuscitation (H/R) may develop a systemic inflammatory response syndrome (SIRS) that leads to dysfunction of vital organs (multiple organ dysfunction syndrome, MODS). SIRS and MODS may involve mitochondrial dysfunction. Under pentobarbital anesthesia, C57BL6 mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution containing minocycline, tetracycline (both 10 mg/kg body weight) or vehicle. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R with vehicle or tetracycline, ALT increased to 4538 U/L and 3999 U/L, respectively, which minocycline decreased to 1763 U/L (P<0.01). Necrosis and TUNEL also decreased from 24.5% and 17.7 cells/field, respectively, after vehicle to 8.3% and 8.7 cells/field after minocycline. Tetracycline failed to decrease necrosis (23.3%) but decreased apoptosis to 9 cells/field (P<0.05). Minocycline and tetracycline also decreased caspase-3 activity in liver homogenates. Minocycline but not tetracycline decreased lipid peroxidation after resuscitation by 70% (P<0.05). Intravital microscopy showed that minocycline preserved mitochondrial polarization after H/R (P<0.05). In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction.
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Author:Christoph Czerny, Andaleb Kholmukhamedov, Tom Prakash Theruvath, Eduardo N. Maldonado, Venkat K. Ramshesh, Mark Lehnert, Ingo Marzi, Zhi Zhong, John J. Lemasters
URN:urn:nbn:de:hebis:30:3-227989
DOI:http://dx.doi.org/doi:10.1155/2012/259512
ISSN:1607-8462
ISSN:0894-8569
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22719175
Parent Title (English):HPB surgery : a world journal of hepatic, pancreatic and biliary surgery
Publisher:Hindawi
Place of publication:New York, NY
Document Type:Article
Language:English
Date of Publication (online):2012/06/08
Year of first Publication:2012
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/06/08
Volume:2012
Issue:Article ID 259512
Pagenumber:9
HeBIS PPN:307595536
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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