BIOREACTIVITY AND BIOCOMPATIBILITY OF A VITAMIN-E-MODIFIED MULTILAYERHEMODIALYSIS FILTER

Background. The present study was designed to test the biocompatibilit y of a new vitamin E-modified multi-layer membrane (CL-E filter), as w ell as its ability to protect against oxygen free radicals during hemo dialysis (HD). Methods. We investigated, both in vitro and in vivo, th e bioreactivity of the filter with respect to the blood antioxidants a nd its ability to prevent lipoperoxidation. The effects on the leukocy te respiratory burst were also studied. Cuprammonium rayon was used as a comparison material (CL-S filter). Results. The in vitro results de monstrated that, under controlled conditions, CL-E is able to preserve blood antioxidants, and particularly vitamin E, from the spontaneous consumption observed in the incubation with CL-S filters and in centra l incubations. In accordance with this observation, the rate of the ox idative demolition of lipids either in plasma and red blood cells (RBC ) or from rat brain homogenate decreased after the exposure to CL-E fi lters in comparison with the CL-S filter. Moreover, in the absence of any significant cytotoxic effects due to both the types of material st udied, the production of oxygen free radicals and nitric oxide (NO) by leukocytes was higher after their in vitro exposure to CL-S, but was quite similar to that of the control leukocytes after exposure to CL-E . In vivo, a one-month treatment with the CL-E filter increased plasma vitamin E by 84.3% with respect to treatment with CL-S; this gain sli ghtly decreased to 68.9% when CL-E treatment was prolonged to three mo nths. In the RBC, vitamin E was found to have increased by 76.7% and 1 13.4% at one and three months, respectively. Plasma glutathione (GSH) levels determined at three months were significantly increased from 0. 10 +/- 0.02 to 0.33 +/- 0.12 mu mol/ml, while the erythrocyte GSH was only slightly increased. The leukocyte function estimated as responsiv eness to soluble chemical stimuli in CL-S-treated patients was signifi cantly improved both qualitatively and qantitatively after CL-E treatm ent. The presence of an increased number of mononuclear cells undergoi ng programmed cell death (apoptosis) in CL-S-treated patients (18.8 +/ - 1.7% vs. a control value of 6.5 +/- 2.3%) as well as the apoptogenic effect of their plasma in vitro on U937 cells was significantly corre cted after CL-E treatment (mean decrease in apoptotic mononuclear cell s at 24 hours of culture, 25.5% and 27.1% at 1 and 3 months, respectiv ely). The anti-apoptogenic effect of CL-E treatment showed a close dep endence on the increase in vitamin E in the blood cell compartment. Co nclusions. This study suggests that this vitamin E-modified membrane c an be considered a highly biocompatible material, the antioxidant prop erties of which can exert a site-specific and timely scavenging functi on against oxygen free radicals in synergy with a hypostimulatory acti on on the PMN respiratory burst.