Antiproliferative activity of Larrea divaricata Cav. on lymphoma cell line: participation of hydrogen peroxide in its action.

Larrea divaricata is a plant used in Argentina. The aim was to analyze the participation of H2O2 in the antiproliferative effect of L divaricata on BW5147 cells. Different studies were performed: proliferation, viability, nitrite production, apoptosis, oxygen reducing activity, NF-kappa B translocation, H2O2 production, H2O2 scavenging activity, and effect on exogenous superoxide dismutase. The extract decreased proliferation and induced apoptosis through P-38 and ERK pathways. The extract activated Mn2+-SOD, increasing H2O2, which was implicated in the antiproliferative mechanism by the increase of Nitric oxide (NO). New drugs, which can increase H2O2, could be a therapeutic strategy for the treatment of cancer.

Effect of streptozotocin on reactive oxygen species and antioxidant enzyme secretion in rat submandibulary glands: a direct and an indirect relationship between enzyme activation and expression.

The salivary glands are important exocrine and endocrine organs, whose role in oral health is well recognized. Also these glands contribute to the maintenance of systemic health. During diabetes an impairment of salivary glands is reported. In this work the oxidative stress produced after 10days of a single dose of streptozotocin administration in rats was observed in submandibulary glands. Under this condition a misbalance of the enzymes with antioxidant activity was observed in glands and in incubation medium, as well as in reactive oxygen species such as hydrogen peroxide (H(2)O(2)), superoxide anion (O(2)(-)) and nitric oxide (NO). An increase of NO and H(2)O(2) and a decrease of O(2)(-) were found. A direct relationship between peroxidase and nitric oxide synthase (iNOS) activities with enzyme expression was recorded, in contrast an inverse relationship between superoxide dismutase activity and expression was observed. If the high level of H(2)O(2) persists in time as well as a low level of peroxidase, oral pathologies are expected to occur. So, under this situation to study the modulation of enzymes involved in reactive oxygen species metabolism during oxidative stress in oral tissues could be very important in the managing of oral pathologies.

Effect of caffeine on the secretion of peroxidase in rat submandibular gland: a study of its mechanism of action.

OBJECTIVE: In this work, we analysed the mechanism of action of caffeine on peroxidase secretion in the female rat submandibular gland. The signaling molecules cAMP and nitric oxide were monitored as potential mediators. DESIGN: The salivary gland peroxidase secretion of female albino Wistar rats was assessed by a spectroscopic method. RESULTS: Caffeine was found to exert an increase on peroxidase secretion in a concentration-response manner: the peroxidase secretion stimulation index (SI) (secreted peroxidase from treated/secreted peroxidase from basal) for caffeine 10 microg/ml: 2.2+/-0.18 (P<0.05); caffeine 100 microg/ml alone: 3+/-0.18 (P<0.01); +LNMMA (LN monomethyl arginine): 1+/-0.1 (P<0.05); caffeine 1000 microg/ml alone: 5+/-0.35 (P<0.01); +LNMMA: 2+/-0.2 (P<0.05). These results were associated with an increase in cAMP and total nitrites production. Total nitrites, SI caffeine 100 microg/ml alone: 2.8+/-0.2 (P<0.01); +LNMMA: 1+/-0.08 (P<0.05); caffeine 1000 microg/ml alone: 4.8+/-0.3 (P<0.01); +LNMMA: 2.3+/-0.18 (P<0.05). CONCLUSION: It could thus be concluded that cAMP and NO are involved in the mechanism of action displayed by caffeine. This is the first report on the mechanism of action of caffeine on peroxidase secretion.

Effect of Larrea divaricata Cav. extract and nordihydroguaiaretic acid upon peroxidase secretion in rat submandibulary glands.

Free radicals are involved in several diseases, including cancer, central nervous system alterations and inflammatory pathologies. Peroxidase is an oral enzyme implicated in the defence of oral cavity. It has been determined that flavonoids and lignans possess antioxidant and free radical scavenging either directly or indirectly, usually by means of increasing the secretion of free radicals scavenger enzymes. Larrea divaricata Cav. is a plant used in folk Argentine medicine for the treatment of cancer and inflammatory ailments. In this study, we have determined the effect and mechanism of action of an aqueous extract of the leaves of L. divaricata and NDGA on peroxidase secretion in female rat submandibular glands. The extract significantly increased the secretion and total peroxidase. % of secreted peroxidase (X +/- S.E.M.): extract maximum response: 150 +/- 10; % of total peroxidase (X +/- S.E.M.): extract maximum response: 1000 +/- 90. The effect of the extract on peroxidase secretion was mediated by beta1 adrenoceptors (% of secreted peroxidase: extract + atenol maximum response: 50 +/- 4 ). Meanwhile, NDGA produced a decrease in peroxidase secretion (peroxidase secreted: basal: 0.44 +/- 0.03; NDGA 2.5 x 10(-6) M: 0.20 +/- 0.02; prostaglandins E2 (PGE2) 10(-7)M: 1.32 +/- 0.5; NDGA + PGE2: 0.46 +/- 0.035), an effect that was exerted by the inhibition on prostaglandins synthesis.