Pro‐oxidant effects of phenothiazine and phenoxazine on erythrocytes in the presence of peroxyl radical

Abstract

Phenothiazine (PtzNH) and phenoxazine (PozNH) can protect human erythrocytes against hemolysis induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), a peroxyl radical supplier. However, an antioxidant may be a pro-oxidant to accelerate the oxidation in the presence of radicals. The aim of this work is to assess whether PtzNH and PozNH have the potential to be pro-oxidants in AAPH-induced hemolysis of human erythrocytes. It has been found that high concentrations of PtzNH and PozNH employed were able to initiate hemolysis even in the absence of AAPH. In the presence of AAPH, the period of PtzNH and PozNH to lag hemolysis (t(lag)) decreased with the increase in the concentrations of PtzNH and PozNH, implicating that high concentration of PtzNH and PozNH accelerated hemolysis. So, PtzNH and PozNH played pro-oxidants' role in this case. Furthermore, high concentrations of AAPH employed made the pro-oxidant effect of PtzNH more remarkable. On the contrary, PozNH played a pro-oxidant role if only low concentration of AAPH was employed.

Phenothiazines: Nrf2 activation and antioxidant effects

“…[ 38 ] Although several PTZs exhibit antioxidant protection to erythrocytes against 2,2‐azobis(2‐ amidinopropane hydrochloride)‐induced hemolysis, Compound 12 exhibits a pro‐oxidant activity only at very high concentrations. [ 39 ] At this level of concentration, Compound 12 is oxidated to phenothiazinyl radical (•PTZ), which in turn permeates erythrocytes and induces radical propagation. As a consequence, fatty acid oxidation occurs in the cellular membrane triggering cytotoxic processes.…”