No abstract

Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells.

To explain a paradoxical radiosensitizing effect of rosmarinic acid (RA) on the melanoma B16F10 cells, we analyzed the glutathione (GSH) intracellular production on this cell (traditionally considered radioresistant) in comparison with human prostate epithelial cells (PNT2) (considered to be radiosensitive). In PNT2 cells, the administration of RA increased the total GSH content during the first 3 h (p < 0.01) as well as increased the GSH/oxidized glutathione (GSSG) ratio in all irradiated cultures during all periods studied (1h and 3h) (p < 0.001), portraying an increase in the radioprotective capacity. However, in B16F10 cells, administration of RA had no effect on the total intracellular GSH levels, decreasing the GSH/GSSG ratio (p < 0.01); in addition, it caused a significant reduction in the GSH/GSSG ratio in irradiated cells (p < 0.001), an expression of radioinduced cell damage. In B16F10 cells, the administration of RA possibly activates the metabolic pathway of eumelanin synthesis that would consume intracellular GSH, thereby reducing its possible use as a protector against oxidative stress. The administration of this type of substance during radiotherapy could potentially protect healthy cells for which RA is a powerful radioprotector, and at the same time, cause significant damage to melanoma cells for which it could act as a radiosensitive agent.

Although different studies have demonstrated different applications of Pycnanthus angolensis extracts in traditional African and Asian medicine, its possible antimutagenic or genoprotective capacities have never been explored. We studied these capabilities of Pycnanthus angolensis seed extract (PASE) by means of the two micronucleus assays, determining the frequency of micronucleus (MN) yield in mouse bone marrow (in vivo) and in human lymphocytes blocked by cytochalasin B (in vitro). PASE exhibited a significant genoprotective capacity (p < 0.001) against X-rays with a protection factor of 35% in both in vivo and in vitro assays. Further, its radioprotective effects were determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability test in two cell lines: one being radiosensitive (i.e., human prostate epithelium (PNT2) cells) and the other being radioresistant (i.e., B16F10 melanoma cells). In the radiosensitive cells, PASE showed a protection factor of 35.5%, thus eliminating 43.8% of X-ray-induced cell death (p < 0.001) and a dose reduction factor of 2.5. In the radioresistant cells, a protection factor of 29% (p < 0.001) with a dose reduction factor of 4 was realized. PASE elicited a greater radioprotective capacity than the substances currently used in radiation oncology and, thus, could be developed as a nutraceutical radioprotectant for workers and patients exposed to ionizing radiation.

No abstract