The study aimed to investigate the effects of small ubiquitin-related modifier (SUMO) specific protease 1 (SENP1) on human PXR-mediated MDR1 transcriptional activity and mRNA expression. Empty vector and expression plasmids, including PXR, SENP1 and SENP1 mutant (SENP1m) were transiently transfected into HepG2 and LS174T cells using Lipo2000. Transcriptional activity was detected by dual luciferase reporter gene assay, and mRNA level was measured using real-time polymerase chain reaction. The results showed that SENP1 could remarkably reduce the rifampicin (RIF)-induced MDR1 reporter activity and mRNA level in hPXR over expressed HepG2 and LS174T cells (P < 0.05), whereas adding SENP1m restored the RIF-induced increases (P < 0.05). These results indicated that SENP1 could repress the RIF-induced hPXR-mediated MDR1 transcriptional activity and mRNA expression.

Objective Pancreatic enzymes may spread into the injured intestine, bloodstream,and cause the cascade of inflammatory reactions. Our objective was to explore trypsin expression in serum and vital organs in septic rats. Methods Trypsin levels in serum, heart, lung and jejunum were tested and compared between Escherichia coli endotoxin injected rats(SS), SS treated with a protease inhibitor (ulinastatin) and control group(SHAM). The correlations between serum trypsin, intestinal proteins and inflammation indices were assessed.Two components of mucosal barrier, i.e. mucin-2 and E-cadherin,were measured to evaluate the intestinal mucosal barrier function. The levels of tumor necrosis factor alpha (TNFα), interleukin-6(IL-6) and neutrophil elastase(NE) were measured to determine the inflammation indices.Results Compared to SHAM group, trypsin levels in serum[(73.71±9.14) ng/ml vs. (12.12±2.36) ng/ml],heart[(51.60±15.06) ng/ml vs. (6.39±3.53) ng/ml],lung [(54.73±5.57) ng/ml vs. (5.24±3.08) ng/ml] and jejunum(1.19 ± 0.48 vs. 0.40 ± 0.12) were significantly higher in SS group (all P<0.05). The level of serum trypsin had negative correlation with mucin-2 and E-cadherin, and positive correlation with TNFα, IL-6 and NE (all P<0.05). In rats treated with ulinastatin, trypsin levels were significantly decreased compared with those in SS group including in serum [(65.79±4.88)ng/ml]], heart [(26.33±12.03)ng/ml], lung [(28.73±14.46) ng/ml] and jejunum (0.80±0.20) (all P<0.05).Serum TNFα[ (247.34±16.97)ng/L vs. (178.78±40.81)ng/L] revealed similar changes in ulinastatin and SS group, whereas mucin-2(0.58 ± 0.14 vs. 0.89 ± 0.17)and E-cadherin(0.11 ± 0.04 vs. 0.23 ± 0.06)were both significantly elevated after administration of ulinastatin (both P<0.05). Conclusion Serum and tissue trypsin is elevated in septic rats. Protease inhibitor ulinastatin protects intestinal function by reducing inflammatory reaction.

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.