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 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.
Author: | Christoph CzernyGND, Andaleb Kholmukhamedov, Tom Prakash Theruvath, Eduardo N. Maldonado, Venkat K. Ramshesh, Mark LehnertGND, Ingo MarziORCiDGND, Zhi Zhong, John J. LemastersGND |
---|---|
URN: | urn:nbn:de:hebis:30:3-227989 |
DOI: | https://doi.org/doi:10.1155/2012/259512 |
ISSN: | 1607-8462 |
ISSN: | 0894-8569 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/22719175 |
Parent Title (English): | HPB surgery |
Publisher: | Hindawi |
Place of publication: | New York, NY |
Contributor(s): | Peter Schemmer |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2012/06/08 |
Year of first Publication: | 2012 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2012/06/08 |
Volume: | 2012 |
Issue: | Art. 259512 |
Page Number: | 9 |
First Page: | 1 |
Last Page: | 9 |
Note: | Copyright © 2012 Christoph Czerny et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
HeBIS-PPN: | 307595536 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 3.0 |