Abstract | BACKGROUND: METHODS: C57Bl/6J mice were subjected to sublethal HS (30% blood loss) and then randomly divided into two groups (n = 13 per group) such as Tub-A group (treatment) and vehicle (VEH) group (control). The Tub-A group was given an intraperitoneal injection of Tub-A (70 mg/kg) dissolved in dimethyl sulfoxide ( DMSO). The VEH group was injected with DMSO (1 μl/g body weight). After 24 h, all mice were subjected CLP followed immediately by another dose of Tub-A or DMSO. Survival was monitored for 10 d. In a parallel study, peritoneal irrigation fluid and liver tissue from Tub-A- or DMSO-treated mice were collected 3 h after CLP. Enzyme-linked immunosorbent assay was performed to quantify activity of the myeloperoxidase and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in the peritoneal irrigation fluid. RNA was isolated from the liver tissue, and real-time polymerase chain reaction was performed to measure relative messenger RNA levels of TNF-α and IL-6. RESULTS: Treatment with Tub-A significantly improved survival compared with that of the control (69.2% versus 15.4%). In addition, Tub-A significantly suppressed myeloperoxidase activity (169.9 ± 8.4 ng/mL versus 70.4 ± 17.4 ng/mL; P < 0.01) and reduced levels of cytokines TNF-α and IL-6 in the peritoneal fluid (TNF-α: 105.7 ± 4.7 versus 7.4 ± 2.4 pg/mL; IL-6: 907.4 ± 2.3 versus 483.6 ± 1.6 pg/mL; P < 0.01) compared with those in the VEH control. Gene expression measured by real-time polymerase chain reaction confirmed that Tub-A inhibits transcription of TNF-α and IL-6. CONCLUSIONS: Tub-A treatment significantly improves survival, attenuates inflammation, and downregulates TNF-α and IL-6 gene expression in a rodent two-hit model.
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Authors | Xin Cheng, Zhengcai Liu, Baoling Liu, Ting Zhao, Yongqing Li, Hasan B Alam |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 197
Issue 1
Pg. 39-44
(Jul 2015)
ISSN: 1095-8673 [Electronic] United States |
PMID | 25837686
(Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Indoles
- tubastatin A
- Hdac6 protein, mouse
- Histone Deacetylase 6
- Histone Deacetylases
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Topics |
- Animals
- Biomarkers
(metabolism)
- Enzyme-Linked Immunosorbent Assay
- Histone Deacetylase 6
- Histone Deacetylase Inhibitors
(therapeutic use)
- Histone Deacetylases
- Hydroxamic Acids
(therapeutic use)
- Indoles
(therapeutic use)
- Injections, Intraperitoneal
- Male
- Mice
- Mice, Inbred C57BL
- Multiple Organ Failure
(etiology, metabolism, mortality, prevention & control)
- Random Allocation
- Real-Time Polymerase Chain Reaction
- Sepsis
(complications, drug therapy, metabolism, mortality)
- Shock, Hemorrhagic
(complications, drug therapy, metabolism, mortality)
- Treatment Outcome
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