HEME OXYGENASE INDUCTION BY UVA RADIATION - A RESPONSE TO OXIDATIVE STRESS IN RAT-LIVER

Heme oxygenase is a key enzyme for heme catabolism and catalyzes the o xidative degradation of heme to form biliverdin IX alpha, an immediate precursor of bilirubin. In order, to shed light on the mechanism by w hich UVA radiation causes oxidative damage, the relationship between h eme oxygenase induction and oxidative stress was studied. HO-1 activit y, lipid peroxidation and generation of active oxygen species (H2O2) w ere measured in rat liver exposed to UVA radiation. Besides, soluble a nd enzymatic antioxidant defenses (GSH, SOD, CAT and GSH-Px) were dete rmined, while bilirubin antioxidant capacity was also evaluated. UVA r adiation markedly increased both lipid peroxidation (180% +/- 7; S.E.M ., n = 9 over control value of 0.1 +/- 0.01 nmol MDA/min per mg prot.) and steady state concentration of hydrogen peroxide (4 +/- 0.03 mu M; S.E.M., n = 9) 3 h after treatment. At the same time, GSH content dec reased to 3.6 +/- 0.2 mu mol/g liver (S.E.M., n = 9) increasing therea fter. Antioxidant enzymes reached minimum values 6 h after UVA treatme nt (SOD: 7.2 +/- 0.2 U/mg protein, CAT: 7.8 +/- 0.2 pmol/mg protein, G SH-Px: 0.088 +/- 0.004 U/mg protein; S.E.M., n = 9), starting to incre ase 12 h after irradiation. HO-1 induction was observed 6 h after UVA irradiation, reaching a maximum value of 2.5 +/- 0.03 U/mg protein (S. E.M., n = 9) 12 h after treatment, and then declined until it reached control levels 24 h after exposure. Administration of bilirubin 2 h be fore UVA irradiation, entirely prevented HO-1 induction, the increase in MDA content and the decrease in GSH levels. This study shows that U VA irradiation leads to oxidative stress as evidenced by increased MDA content and H2O2 steady state levels, and depletion of GSH, SOD, CAT and GSH-Px. All these changes produced HO-1 induction. It is concluded that the induction of this enzyme could be a response to oxidative st ress, since bilirubin can act as a physiological antioxidant. (C) 1998 Elsevier Science Ltd. All rights reserved.