Abstract

Nordihydroguaiaretic acid (NDGA) is an antioxidant phenolic lignan isolated from Larrea tridentata. NDGA induces heme oxygenase-1 (HO-1) in renal epithelial (LLC-PK1) cells and in murine embryonic fibroblasts (MEFs). The signaling pathways phosphatidyl inositol 3 kinase (PI3K)/Akt1, p38 and c-Jun N-terminal kinase (JNK) are involved in HO-1 induction in MEFs. The signaling pathway involved in HO-1 induction in LLC-PK1 cells was analyzed in this work. The effect of NDGA on Akt1, extracellular-signal-regulated kinase 1/2 (ERK1/2), p38 and JNK phosphorylation was evaluated by immunoblotting. In addition, the role of the signaling pathways on NDGA induced HO-1 expression and cytoprotection against H₂O₂ in LLC-PK1 cells was assessed by using protein kinase inhibitors. NDGA induced PI3K/Akt1 and ERK1/2 and the inhibition of PI3K/Akt1 prevented HO-1 induction and the NDGA-induced cytoprotection against H₂O₂-induced cell death. Results suggested that PI3K/Akt1was involved in HO-1 induction and cytoprotection induced by NDGA in LLC-PK1 cells.

Key words: Heme oxygenase-1 (HO-1), antioxidant, cytoprotection, PI3K/Akt1 signaling pathways.