Plant extracts and isolated compounds can modulate hydrogen peroxide (H2O2) controlling lymphocytes proliferation.

ROBERTO DAVICINO; GRACIELA FERRARO; CLAUDIA ANESINI

Buenos Aires

Workshop; Oxidative Stress and Antioxidant; 2009

Facultad de Farmacia y Bioquímica y CONICET

Larrea divaricata Cav. (Zygophyllaceae) aqueous extract (LAE) has a well documented antioxidant activity as well as D-limonene (L), a common monoterpene in nature. The aim of this work is to demonstrate the participation of H2O2 (known to be related to the control of cell proliferation) in normal (NL) and tumoral lymphocytes (BW 5147) (TL) proliferation, analysing the role of nitric oxide (NO) and NFêB in its action and to study the effect of LAE and L on H2O2 metabolism by  peroxidase (Px), catalase (CAT) and superoxide dismutase (Mn2+SOD).| H2O2 inhibited (10-5 M to 10-3 M) and increased (10-7 to 10-13 M) NL and TL proliferation. The inhibitory action was related to ERK and P38 pathway, NO production, through NFêB translocation, and apoptosis. TL presented high rate of proliferation associated with a high level of superoxide anion (O2.- ) and low level of H2O2 in relation with low SOD and high Px activities in comparison with NL. On TL, LAE and L (at low concentrations) decreased proliferation and induced apoptosis through P-38 and ERK pathways, related to an increase of NO and H2O2  by Mn2+SOD activation. L at high concentrations, increased NO by the inhibition of protein farnesylation and O2.- production. On NL, L increased cell proliferation and cell viability decreasing H2O2 level through the activation of CAT and Px activities. It is possible that the modulation exert by natural products on H2O2 level could be a therapeutic strategy for the treatment of cancer and could also protect normal lymphocytes from this disease.