ABSTRACT
This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.
Subject(s)
Adjuvants, Pharmaceutic/pharmacology , Curcumin/analogs & derivatives , Curcumin/pharmacokinetics , Enzyme Inhibitors/pharmacokinetics , Intestinal Absorption , Intestine, Small/metabolism , 2,4-Dinitrophenol/pharmacokinetics , ATP-Binding Cassette Transporters/antagonists & inhibitors , Animals , Chromatography, High Pressure Liquid/methods , Curcumin/chemistry , Diarylheptanoids , Emulsions , Female , Intestinal Absorption/drug effects , Intestine, Small/drug effects , Male , Multidrug Resistance-Associated Protein 2 , Multidrug Resistance-Associated Proteins/analysis , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Perfusion Imaging/methods , Probenecid/pharmacology , Rats, Sprague-Dawley , Reference Values , Reproducibility of Results , Time Factors , Uncoupling Agents/pharmacology , Verapamil/pharmacologyABSTRACT
This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.
Subject(s)
Animals , Male , Female , Adjuvants, Pharmaceutic/pharmacology , Curcumin/analogs & derivatives , Curcumin/pharmacokinetics , Enzyme Inhibitors/pharmacokinetics , Intestinal Absorption , Intestine, Small/metabolism , Reference Values , Time Factors , Uncoupling Agents/pharmacology , Verapamil/pharmacology , Probenecid/pharmacology , Reproducibility of Results , Chromatography, High Pressure Liquid/methods , Rats, Sprague-Dawley , ATP-Binding Cassette Transporters/antagonists & inhibitors , 2,4-Dinitrophenol/pharmacokinetics , Curcumin/chemistry , Multidrug Resistance-Associated Proteins/analysis , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Emulsions , Perfusion Imaging/methods , Intestinal Absorption/drug effects , Intestine, Small/drug effectsABSTRACT
The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.
Subject(s)
Animals , Male , Lymph/metabolism , Mesenteric Vascular Occlusion/complications , Reperfusion Injury/etiology , Reperfusion/adverse effects , Spleen/injuries , Acute-Phase Proteins/analysis , Adenosine Triphosphatases/analysis , /analysis , Carrier Proteins/analysis , Endotoxins/analysis , Intercellular Adhesion Molecule-1/analysis , Intestines/blood supply , Mesenteric Artery, Superior , Malondialdehyde/analysis , Membrane Glycoproteins/analysis , Nitric Oxide Synthase/analysis , Nitric Oxide/analysis , Peroxidase/analysis , Rats, Wistar , Spleen/pathology , Superoxide Dismutase/analysis , Tumor Necrosis Factor-alpha/analysisABSTRACT
This study investigated cadherin-1 (Cdh1) expression in the sensorimotor cortex of rats after spinal cord injury (SCI). The repairing effect of Cdh1 was evaluated by silencing its expression with lentivirus-mediated RNAi. Twenty male Sprague-Dawley (SD) rats were randomly divided into a normal group and an operation group. Rats of the operation group were given SCI by the Allen method (T10-T11). Cdh1 expression in the sensorimotor cortex was examined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis. Thirty male SD rats were divided into a sham-operation (SO) group, a lentivirus vector (LV) group, and a recombinant lentivirus (RL) group. Rat behavior was evaluated using the Basso-Beattie-Bresnahan (BBB) test every week. Ten days after injection, Cdh1 expression was examined by quantitative real-time PCR and Western blot. Six weeks after injury, animals were injected with biotinylated dextran amine-Texas Red (BDA-TR), and then at 8 weeks, spinal cords were removed and sectioned in serial order. The expression of Cdh1 mRNA was significantly higher in the operation than in the normal group (P < 0.05). The expression of Cdh1 mRNA was lower in the RL than in the SO or LV groups at 10 days after injection (P < 0.05). In addition, the BBB score was higher for the RL than for the SO or LV groups at 6 weeks after injury (P < 0.05). A novel population of BDA-labeled axons was observed extending past the lesion in the RL group, which was rarely observed in the SO and LV groups. These results suggest that the anaphase-promoting complex-Cdh1 may play an important role in inhibiting axonal growth.