Minocycline Decreases Liver Injury after Hemorrhagic Shock and Resuscitation in Mice. (7th June 2012)

• Record Type: Journal Article
• Authors: Czerny, Christoph; Kholmukhamedov, Andaleb; Theruvath, Tom P.; Maldonado, Eduardo N.; Ramshesh, Venkat K.; Lehnert, Mark; Marzi, Ingo; Zhong, Zhi; Lemasters, John J.
• Other Names: Schemmer Peter Academic Editor.
• Is Part Of: HPB surgery. Volume 2012(2012)
• Publication Date: 2012-06-07
• Subjects: Biliary tract -- Surgery -- Periodicals; Liver -- Surgery -- Periodicals; Pancreas -- Surgery -- Periodicals; 617.55
• DOI: 10.1155/2012/259512
• Languages: English
• ISSNs: 0894-8569

Abstract

Abstract : 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.