Differential expression of c-jun, c-fos and hsp 70 mRNAs after folic acid and ischemia-reperfusion injury: effect of antioxidant treatment.

The regenerative repair response to folic acid and ischemia-reperfusion injury is characterized by different patterns of renal tubular cell proliferation. The purpose of this study was to examine the time course of the expression of two early growth response genes, c-jun and c-fos, and of the stress response gene hsp70 after such renal injuries and to determine the role played by reactive oxygen species generated during reperfusion, on gene induction. Ischemic injury caused an almost immediate increase of c-jun, c-fos and hsp70 mRNA expression, that reached a maximum at 1 h of reperfusion. Folic acid treatment increased c-fos and hsp70 mRNAs at 2 h, while c-jun accumulated at 1 h, although to a lesser extent. The intravenous administration of two antioxidant drugs, allopurinol or dimethyl sulfoxide (DMSO), 20 min before ischemia, to prevent the generation of oxygen free radicals during reperfusion, did not cause any change in gene expression. In contrast, the combined administration of allopurinol and DMSO reduced c-jun and c-fos mRNA expression as well as tubular cell damage at 1 h of reperfusion, although not at earlier times while hsp70 mRNA expression remained almost unchanged. Taken together, the results suggest that these scavengers, by reducing reactive oxygen species and renal damage during reperfusion, may affect the expression and/or persistence of transcripts involved in the control of epithelial cell proliferation.