Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis.

OBJECTIVE: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. METHODS: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 ß, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 ß were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. RESULTS: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 ß, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). CONCLUSIONS: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.

Arteriovenous Graft for Hemodialysis: Effect of Cryotherapy on Postoperative Pain and Edema.

BACKGROUND: Arteriovenous grafting offers an alternative for patients whose vessels are unsuitable for arteriovenous fistula. However, as a result of subcutaneous tunnel dissection, postoperative pain and edema of the operated limb present early after surgery. As a traditional therapeutic approach, cryotherapy has the ability to suppress postoperative pain and edema. AIMS: The purpose of the study was to investigate the feasibility of cryotherapy after arteriovenous graft surgery to decrease perioperative medication usage. DESIGN: This study was a randomized controlled trial. SETTING: A large integrated health care facility in South China. PARTICIPANTS/SUBJECTS: A total of 85 hemodialysis patients who received arteriovenous graft surgery from March 2011 to February 2017 were enrolled. METHODS: The participants were divided into an intervention group and a control group according to the postoperative management. Ice packs were applied covering the operative forearm for 120 minutes after wound closure in the intervention group. General information, pain score, analgesic consumption, wound inflammation, forearm edema, and participant satisfaction were compared between the two groups. RESULTS: Cryotherapy-treated patients required less analgesia (26.19% vs. 48.84%, p < .05), reported lower pain score from 30 minutes to 48 hours postoperative (p < .05), less wound inflammation (11.90% vs. 25.58%, p < .05), and higher participant satisfaction (8.92 ± 0.57 vs. 6.52 ± 0.63, p < .05), whereas the incidence of forearm edema was equivalent (p > .05). No adverse events were reported in either group. CONCLUSIONS: Cryotherapy is a preferable intervention for patients after arteriovenous graft implantation as a result of its favorable cost, convenience, and fewer side effects.

Cryotherapy Relieves Pain and Edema After Inguinal Hernioplasty in Males With End-Stage Renal Disease: A Prospective Randomized Study.

CONTEXT: Tension-free hernioplasty under local anesthetic infiltration is a reasonable choice for end-stage renal disease patients with hernia. OBJECTIVES: The purpose of the study was to investigate the feasibility of cryotherapy after hernioplasty surgery to relieve pain and scrotal edema. METHODS: This was a prospective, randomized, and controlled trial held in a large integrated health care facility in South China. One hundred sixty-nine male patients on hemodialysis and scheduled for hernioplasty were enrolled between March 2013 and February 2017. The participants were divided into an intervention group and a control group. In the intervention group, ice packs were applied after surgery. Demographic information, vital signs, pain score, opioid consumption, wound inflammation, scrotal edema, and patient satisfaction were compared between the two groups. The primary outcome was pain score. RESULTS: Cryotherapy-treated patients required less opioid consumption (5.95 vs. 15.29 mg; P < 0.05), reported lower pain scores from 30 minutes to 48 hours after operation (P < 0.05), less wound inflammation (11.90 vs. 32.94%; P < 0.05), lower incidence of scrotal edema in the first and second days (P < 0.05), and higher patient satisfaction (8.95 vs. 6.50 cm; P < 0.05), with stable vital signs throughout the monitoring period (P > 0.05). CONCLUSION: Owing to its favorable cost, convenience, and low frequency of adverse effects, cryotherapy is useful for end-stage renal disease populations after hernioplasty to relieve pain and scrotal edema.