Prevention of oxidation and apoptosis in human peripheral blood mononuclear cells exposed to calcium dobesilate

Abstract

The antioxidant effects of calcium dobesilate (CD) (Doxium®) were investigated in relation to the oxidative status, apoptosis, andin vitro proliferation of human peripheral blood mononuclear cells (PBMC) isolated from healthy donors. Calcium dobesilate alone did not modify cell growthin vitro until it reached 10 μM. This molecule counteracted oxidative damage generated by the highly reducing sugar 2-deoxy-D-ribose (dR) and was shown to reduce apoptosis by delaying both membrane permeability changes and DNA fragmentation. Calcium dobesilate (10 μM) was effective in a time-dependent manner on several parameters, representative of the cellular oxidative status. In particular, CD significantly increased the activity of glutathione S-transferase (GST) after 3 days of treatment and also the activity of γ-glutamyltransferase (γ-GT). Both of these enzymes are known to be involved in the glutathione (GSH) metabolic cycle. This enzymatic behavior was reversed after 7 days of treatment, with a significant GST decrease and a γ-GT activation. After 7 days of CD exposure, the intracellular GSH content was enhanced and this resulted in a dramatic decrease of lipid peroxidation, underlining the powerful antioxidant properties of CD in human PBMC.