High Concentration of C5a-Induced Mitochondria-Dependent Apoptosis in Murine Kidney Endothelial Cells.

Patients with a relapse of idiopathic nephrotic syndrome have significantly increased levels of serum complement component 5a (C5a), and proteinuria has been noted in mice treated with C5a via changes in permeability of kidney endothelial cells (KECs) in established animal models. However, the apoptosis of KECs treated with high concentrations of C5a has also been observed. As mitochondrial damage is known to be important in cell apoptosis, the aim of this study was to examine the association between C5a-induced mouse KEC apoptosis and mitochondrial damage. Mouse KECs were isolated and treated with different concentrations of C5a. Cell viability assays showed that a high-concentration mouse recombinant protein C5a (rmC5a) treatment reduced mouse KEC growth. Cell cycle phase analysis, including apoptosis (sub-G1 phase) showed an increased percentage of the subG1 phase with a high-concentration rmC5a treatment. Cytochrome c and caspase 3/9 activities were significantly induced in the mouse KECs after a high-dose rmC5a (50 ng/mL) treatment, and this was rescued by pretreatment with the C5a receptor (C5aR) inhibitor (W-54011) and N-acetylcysteine (NAC). Reactive oxygen species (ROS) formation was detected in C5a-treated mouse KECs; however, W-54011 or NAC pretreatment inhibited high-dose rmC5a-induced ROS formation and also reduced cytochrome c release, apoptotic cell formation, and apoptotic DNA fragmentation. These factors determined the apoptosis of mouse KECs treated with high-dose C5a through C5aR and subsequently led to apoptosis via ROS regeneration and cytochrome c release. The results showed that high concentrations of C5a induced mouse KEC apoptosis via a C5aR/ROS/mitochondria-dependent pathway. These findings may shed light on the potential mechanism of glomerular sclerosis, a process in idiopathic nephrotic syndrome causing renal function impairment.

Effects of fish oil on inflammatory modulation in surgical intensive care unit patients.

BACKGROUND: The benefit of ω-3 fatty acids in fat emulsion remains controversial. This study evaluated the effect of ω-3 fatty acids on immune and inflammatory modulation in surgical intensive care unit (SICU) patients. METHODS: Thirty-eight patients admitted to the SICU after major surgery were enrolled in this prospective controlled study and randomized to receive parenteral nutrition (PN) with equal volume and calories from glucose, nitrogen, and fat but different lipid components for 7 postoperative days. Group A (n = 12) received a mixture of soybean and medium-chain triglyceride oils; group B (n = 18) received a fat emulsion with part of the lipid replaced by fish oil. Blood tests, including lipid profile, routine biochemistry, inflammatory cytokines, and lymphocyte subpopulations, were evaluated preoperatively and on postoperative days 4 and 7. RESULTS: Both lipid regimens were well tolerated. There was a trend toward reduced serum inflammatory cytokines in group B vs group A with significant differences regarding interleukin (IL)-1, IL-8, and interferon (IFN)-γ on postoperative day 4 (P < .05) and IL-1, IL-8, IFN-γ, IL-6, and tumor necrosis factor-α on postoperative day 7 (P < .05). There was a reduction in postoperative liver dysfunction (A vs B: 50% vs 33.3%) and infection rate (A vs B: 41.7% vs 27.8%) in group B, although this was not statistically significant. There was no mortality in either group. CONCLUSION: This study suggests that supplementation of parenteral ω-3 fatty acids in PN is safe and may improve immune and hyperinflammatory response for SICU patients after major surgery.