Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin

During continuous ambulatory peritoneal dialysis (CAPD) the peritoneal immu ne cells, mainly macrophages, are highly compromised by multiple factors in cluding oxidative stress, resulting in a loss of functional activity. One r eason for the increase of inflammatory reactions could be an imbalance in t he thiol-disulfide status. Here, the possible protective effects of the ant ioxidant flavonoid complex silymarin and its major component silibinin on t he cellular thiol status were investigated. Peritoneal macrophages from dia lysis fluid of 30 CAPD patients were treated with silymarin or silibinin up to 35 days. A time-dependent increase of intracellular thiols was observed with a nearl y linear increment up to 2.5-fold after 96 hours, reaching a maximum of 3.5 -fold after 20 days of culture. Surface-located thiols were also elevated. The stabilization of the cellular thiol status was followed by an improveme nt of phagocytosis and the degree of maturation as well as significant chan ges in the synthesis of IL-6 and IL-1ra. Furthermore, the treatment of peri toneal macrophages with flavonoids in combination with cysteine donors resu lted in a shortened and more efficient time course of thiol normalization a s well as in a further increased phagocytosis. In addition, GSH-depletion i n thiol-deficient media simulating CAPD procedures led to intracellular thi ol deficiency similar to the in vivo situation. It is concluded that treatment with milk thistle extracts silymarin and sil ibinin alone or, more effectively in combination with cysteine donors, prov ide a benefit for peritoneal macrophages of CAPD-patients due to a normaliz ation and activation of the cellular thiol status followed by a restoration of specific functional capabilities.