cytochrome-c-t and Edema

We describe several novel curcumin analogues that possess both anti-inflammatory antioxidant properties and thrombolytic activities. The therapeutic efficacy of these curcumin analogues was verified in a mouse ear edema model, a rat arterial thrombosis assay, a free radical scavenging assay performed in PC12 cells, and in both in vitro and in vivo ischemia/reperfusion models. Our findings suggest that their protective effects partially reside in maintenance of optimal mitochondrial function.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Cytochromes c; Disease Models, Animal; Edema; Enzyme-Linked Immunosorbent Assay; Free Radical Scavengers; Human Umbilical Vein Endothelial Cells; Interleukin-6; Mice; Microscopy, Fluorescence; Mitochondria; Muscle, Skeletal; Oxidative Stress; PC12 Cells; Quantum Theory; Rats; Reactive Oxygen Species; Reperfusion Injury; Tumor Necrosis Factor-alpha

To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine.. Prospective, randomized, controlled study.. Research laboratory.. Sprague Dawley rats.. Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine).. In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Δψm), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorβ, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and PaCO2 were significantly increased, and oxygen (PaO2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure.. Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar epithelial cell from bilirubin-induced injury. Dexmedetomidine may be a good choice of anesthetic/sedative for patients with chronic liver disease during the perioperative period.

Topics: Adrenergic alpha-2 Receptor Antagonists; Animals; Apoptosis; Cell Culture Techniques; Cell Cycle; Cytochromes c; Dexmedetomidine; Edema; Epithelial Cells; Humans; Hyperbilirubinemia; Membrane Potential, Mitochondrial; Prospective Studies; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley

The reactions of ruthenium(III) chloride trihydrate with piroxicam (H2PIR) and tenoxicam (H2TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru(III)Cl2(H2PIR)(HPIR)],·1, and [Ru(III)Cl2(H2TEN)(HTEN)],·2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line, Tumor; Cell Survival; Coordination Complexes; Cytochromes c; Drug Stability; Edema; Hindlimb; Humans; Ligands; Male; Muramidase; Piroxicam; Protein Binding; Quantum Theory; Rats; Rats, Wistar; Ruthenium Compounds; Serum Albumin; Solubility

Amyotrophic lateral sclerosis (ALS) is a devastating disorder involving loss of movement due to degeneration of motor neurons. Studies suggest that in ALS axonal dysfunction precedes the death of motor neurons. Pathologically, ALS is characterized by neurofilamentous swellings (spheroids) within the axons of motor neurons. However, the causes of this axonopathy and possible resulting axonal dysfunction are not known. Using a novel model of cultured mouse motor neurons, we have determined that these neurons are susceptible to proximal axonopathy, which is related to the glial environment. This axonopathy showed remarkable similarity, both morphologically and neurochemically, to spheroids that develop over months in SOD1(G93A) transgenic mice. Focal ubiquitination, as well as perturbations of neurofilaments and microtubules, occurred in the axonal spheroid-like swellings in vitro, and visualization of mitochondrial dynamics demonstrated that axonopathy resulted in impaired axonal transport. These data provide strong evidence for the involvement of non-neuronal cells in axonal dysfunction in ALS. This cell culture model may be of benefit for the development of therapeutic interventions directed at axonal preservation.

Topics: Amyotrophic Lateral Sclerosis; Animals; Animals, Newborn; Axons; Bacterial Proteins; Cell Death; Cells, Cultured; Cytochromes c; Cytoskeleton; Disease Models, Animal; Edema; Glial Fibrillary Acidic Protein; Humans; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons; Neurofilament Proteins; Neuroglia; Spinal Cord; Superoxide Dismutase; Synaptophysin; Time Factors; Transfection