stilbenes and Systemic-Inflammatory-Response-Syndrome

Heterotopic ossification (HO) develops in the extremities of wounded service members and is common in the setting of high-energy penetrating injuries and blast-related amputations. No safe and effective prophylaxis modality has been identified for this patient population. Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO. The purpose of this study was to determine the effects of Palovarotene on inflammation, progenitor cell proliferation, and gene expression following a blast-related amputation in a rodent model (n = 72 animals), as well as the ability of Raman spectroscopy to detect early HO before radiographic changes are present. Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL-6 (p = 0.01), TNF-α (p = 0.001), and IFN-γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post-operative day (POD)-7 (p = 0.03). Palovarotene decreased osteogenic connective tissue progenitor (CTP-O) colonies by as much as 98% both in vitro (p = 0.04) and in vivo (p = 0.01). Palovarotene treated animals exhibited significantly decreased expression of osteo- and chondrogenic genes by POD-7, including BMP4 (p = 0.02). Finally, Raman spectroscopy was able to detect differences between the two groups by POD-1 (p < 0.001). These results indicate that Palovarotene inhibits traumatic HO formation through multiple inter-related mechanisms including anti-inflammatory, anti-proliferative, and gene expression modulation. Further, that Raman spectroscopy is able to detect markers of early HO formation before it becomes radiographically evident, which could facilitate earlier diagnosis and treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1135-1144, 2018.

Topics: Animals; Blast Injuries; Cell Proliferation; Chondrogenesis; Drug Evaluation, Preclinical; Gene Expression; Male; Multipotent Stem Cells; Ossification, Heterotopic; Osteogenesis; Pyrazoles; Rats, Sprague-Dawley; Spectrum Analysis, Raman; Stilbenes; Systemic Inflammatory Response Syndrome; War-Related Injuries

The literature on resveratrol in severe acute pancreatitis (SAP) is limited though it has been widely studied in infections and trauma. The aim of this study was to investigate the inhibitory effect of resveratrol on inflammatory responses in a rat model of SAP.. Male Sprague-Dawley (SD) rats were randomly divided into 3 groups: SAP group, resveratrol group and control group. 4.0% sodium taurocholate was injected into the pancreatic duct to induce SAP. In the resveratrol group, resveratrol (10 mg/kg) was injected through penal vein 5 min after SAP was induced. The peritoneal macrophages of the rats were collected 3, 6 and 12 h after stimulus and then incubated for 24 h. The expression of nuclear factor kappa B (NF-kappaB) and inducible nitric oxide synthase (iNOS) in peritoneal macrophages was measured. The levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) in culture medium of peritoneal macrophages and serum of rats were evaluated.. Histological examination of pancreas indicated that the damage in the SAP group was more severe than that in the resveratrol group. The expression of NF-kappaB and iNOS in peritoneal macrophages was significantly higher in the SAP group than in the resveratrol group. The concentrations of TNF-alpha, IL-1 and NO in culture medium and serum were significantly elevated in the SAP group when compared with the resveratrol group.. The inhibiting effect on the inflammatory response and the decreased expression of TNF-alpha, IL-1 and NO in peritoneal macrophages suggest resveratrol as a novel anti-inflammatory agent for reducing the severity of SAP.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Culture Media; Disease Models, Animal; Interleukin-1; Macrophages, Peritoneal; Male; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Pancreatitis; Random Allocation; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Systemic Inflammatory Response Syndrome; Time Factors; Tumor Necrosis Factor-alpha