Nitric oxide is synthesized in acute leukemia cells after exposure to phenolic antioxidants and initially protects against mitochondrial membrane depolarization

We investigated the early events involved in loss of mitochondrial membrane potential (ΔΨmt) leading to apoptosis in cells derived from patients with acute lymphocytic leukemia after exposure to phenolic antioxidants. Using the nitric oxide binding dye diaminofluorescein-FM diacetate, we found that intracellular nitric oxide (NO) levels increased significantly within 4 h after exposure to the antioxidants curcumin, carnosol, and quercetin. Inhibition of nitric oxide synthetase (NOS) activity with mercaptoethylguanidine increased the percentage of leukemia cells with depolarized mitochondria membranes after antioxidant treatment. These data suggest that NO production in the leukemia-derived cells may be a protective response to maintain ΔΨmt after antioxidant exposure and inhibition of NOS increases the disruption of mitochondrial homeostasis induced by the antioxidants.