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Minocycline decreases liver injury after hemorrhagic shock and resuscitation in mice.

Czerny C, Kholmukhamedov A, Theruvath TP, Maldonado EN, Ramshesh VK, Lehnert M, Marzi I, Zhong Z, Lemasters JJ - HPB Surg (2012)

Bottom Line: 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.In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Death, Injury & Regeneration, Department of Pharmaceutical & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Minocycline decreases necrosis after hemorrhage and resuscitation. H/R was performed, as described in Figure 1. Necrosis was assessed by H&E histology at 6 h after sham operation (a) or resuscitation with vehicle, minocycline, or tetracycline (b–d). In (e), necrosis as percent area in liver sections was averaged from 5 livers per treatment group. Necrosis in sham-operated mice was absent and not plotted. *, central vein. Bar is 100 μm. *P < 0.05 versus vehicle and tetracycline.
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fig2: Minocycline decreases necrosis after hemorrhage and resuscitation. H/R was performed, as described in Figure 1. Necrosis was assessed by H&E histology at 6 h after sham operation (a) or resuscitation with vehicle, minocycline, or tetracycline (b–d). In (e), necrosis as percent area in liver sections was averaged from 5 livers per treatment group. Necrosis in sham-operated mice was absent and not plotted. *, central vein. Bar is 100 μm. *P < 0.05 versus vehicle and tetracycline.

Mentions: Liver injury was also assessed histologically at 6 h postoperatively. In sham-operated mice, liver histology was normal and indistinguishable from untreated mice (Figure 2(a) and data not shown). After H/R with vehicle and tetracycline treatments, large areas of necrosis developed 6 h postoperatively with a predominately pericentral and midzonal distribution, which was decreased after resuscitation with minocycline (Figures 2(b)–2(d)). Resuscitation with minocycline decreased hepatic necrosis from 24.5 ± 1.5% after vehicle to 8.3 ± 1.4% (P < 0.05) (Figure 2(e)). By contrast, resuscitation with tetracycline did not decrease liver necrosis after H/R (23.3 ± 1.5%) in comparison to vehicle treatment. Overall, minocycline treatment decreased hepatic necrosis by nearly two-thirds.


Minocycline decreases liver injury after hemorrhagic shock and resuscitation in mice.

Czerny C, Kholmukhamedov A, Theruvath TP, Maldonado EN, Ramshesh VK, Lehnert M, Marzi I, Zhong Z, Lemasters JJ - HPB Surg (2012)

Minocycline decreases necrosis after hemorrhage and resuscitation. H/R was performed, as described in Figure 1. Necrosis was assessed by H&E histology at 6 h after sham operation (a) or resuscitation with vehicle, minocycline, or tetracycline (b–d). In (e), necrosis as percent area in liver sections was averaged from 5 livers per treatment group. Necrosis in sham-operated mice was absent and not plotted. *, central vein. Bar is 100 μm. *P < 0.05 versus vehicle and tetracycline.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3375163&req=5

fig2: Minocycline decreases necrosis after hemorrhage and resuscitation. H/R was performed, as described in Figure 1. Necrosis was assessed by H&E histology at 6 h after sham operation (a) or resuscitation with vehicle, minocycline, or tetracycline (b–d). In (e), necrosis as percent area in liver sections was averaged from 5 livers per treatment group. Necrosis in sham-operated mice was absent and not plotted. *, central vein. Bar is 100 μm. *P < 0.05 versus vehicle and tetracycline.
Mentions: Liver injury was also assessed histologically at 6 h postoperatively. In sham-operated mice, liver histology was normal and indistinguishable from untreated mice (Figure 2(a) and data not shown). After H/R with vehicle and tetracycline treatments, large areas of necrosis developed 6 h postoperatively with a predominately pericentral and midzonal distribution, which was decreased after resuscitation with minocycline (Figures 2(b)–2(d)). Resuscitation with minocycline decreased hepatic necrosis from 24.5 ± 1.5% after vehicle to 8.3 ± 1.4% (P < 0.05) (Figure 2(e)). By contrast, resuscitation with tetracycline did not decrease liver necrosis after H/R (23.3 ± 1.5%) in comparison to vehicle treatment. Overall, minocycline treatment decreased hepatic necrosis by nearly two-thirds.

Bottom Line: 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.In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Center for Cell Death, Injury & Regeneration, Department of Pharmaceutical & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.

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.

No MeSH data available.


Related in: MedlinePlus