Influence of gamma-rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs

Purpose: Phenothiazine drugs have been found to sensitize hypoxic cancer ce lls while offering protection to normal cells. Since phenothiazines are kno wn to induce the cytochrome P450 system, its radiomodulation by phenothiazi nes has been examined. Materials and methods: Mice were administered phenothiazines intraperitonea lly and irradiated with different doses of gamma-rays at 1.38 Gy/min. The a ctivities of NADPH-cytochrome P450 reductase and NADH-cytochrome b(5) reduc tase, the content of cytochrome P450 and b(5), the extent of lipid peroxida tion as well as the activities of LDH, XO, SOD, GST and DTD were determined in the liver. Results: The levels of different components of the cytochrome P450 system a nd antioxidant enzymes were enhanced up to 5 Gy and decreased thereafter. H owever, a progressive increase was noticed in peroxidative damage and the a ctivities of LDH and XO. Administration of phenothiazines enhanced the radi ation effect on components of the cytochrome P450 system (except NADH-cytoc hrome b(5) reductase) and the activities of SOD, GST and DTD. Concomitantly , phenothiazines inhibited lipid peroxidation, LDH and XO. Conclusions: Activation of the cytochrome P450 system by phenothiazines lea ding to the enhancement of antioxidant potential of animals and free-radica l scavenging are attributes of the radioprotective action of phenothiazines .