Conclusion
Our results indicated that HDACI classes I and IIb and non-selective HDACI can significantly prolong survival. Moreover, non-selective and isoform-specific class I and IIa/IIb HDACIs can attenuate inflammation and organ injury.
Methods
Experiment I, SD rats were subjected to cecal ligation and puncture and randomly assigned to the no treatment, dimethyl sulfoxide (DMSO) only, MS-275, LMK-235, tubastatinA (TubA), trichostatin-A (TSA), and sirtinol groups (n = 5). Survival was monitored for 48 h. Experiment II, the animals were monitored for 12 h, then, blood and tissues sample were collected. Interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) expressions were evaluated using ELISA. Liver, heart and lung tissues were analysed via hematoxylin and eosin staining. Liver and heart tissue lysates were analysed for acetylated histones H3, H4, a-tubulin and nuclear factor kappa B (NF-κB), IL-6, IL-1β, and TNF-α using western blotting. Splenocytes were examined via flow cytometry to analyse the immune cell population.
Results
MS-275, TubA and TSA treatments significantly prolonged survival. MS-275, LMK-235, TubA and TSA significantly reduced the histopathological scores and AST, ALT, CK, LDH, IL-6, IL-1β and TNF-α levels, significantly increased acetylated of NF-κB and changed the immune cell proportion.