[ role of 6-aminonicotinamide in the resistance of peritoneal macrophages against Leishmania major infection in BALB/c mouse]

The objective of this study was to investigate the relationship between glucose-6-phosphate dehydrogenase inhibition in macrophages treated with 6-Aminonicotinamide, the amount of nitric oxide [NO] production and the resistance of infected macrophages against Leishmania major infection. Peritoneal macrophages of BALB/c mice were isolated and treated with different concentrations [1.25, 2.5, 5, 10 mM] of 6-aminonicotinamide. After 24 hours, the viability of treated macrophages was measured by MTT assay at 540 nm. G6PD activity was measured in the cell extracts 24 hours later. Macrophages were then infected with leishmanial amastigotes and after 18 hours NO production was determined using Griess-reagent. In order to study the inhibition of macrophage activity, 5 mM concentration of 6-AN was used and number of leishmanial amastigotes was recorded in these cells from day 1 to7. Different concentrations of 6-AN were shown to cause a significant increase in cell death and decrease in G6PD activity and NO production in macrophages. Also, the number of amastigotes in macrophages was increased significantly [p < 0.05]. He concentration of 6-aminonicotinamide and G6PD activity affect the viability of BALB/c mice peritoneal macrophages through production of NO. Inhibition of G6PD activity leads to decreased leishmani-cidal activity of mouse peritoneal macrophages

Contribution of oxidative stress to radiosensitization by a combination of 2-DG and 6-AN in human cancer cell line.

In the present studies, the role of oxidative stress in radiosensitization by a combination of 2-DG and 6-aminonicotinamide (6-AN) was examined in a human glioma cell line (BMG-1: wild type p53). Presence of 2-DG or 6-AN for 4 hr after irradiation (gamma ray 2.5 Gy) significantly enhanced the radiation-induced cell death by 18% and the combination (2-DG + 6-AN) enhanced the cell death by 35%. Neither 2-DG nor 6-AN had any further significant effect on the glutathione levels in irradiated cells. However, the combination (2-DG + 6-AN) caused a significant decrease in GSH content, increase in GSSG levels, and enhanced the superoxide radical generation under these conditions. The enhanced cell death caused by the combination (2-DG + 6-AN) mainly resulted by the process of apoptosis as revealed by annexin V binding and was associated with elevated levels of Cyclin B1. However, no significant change was observed in the levels of Bcl-2. Thus, for the first time, our results have demonstrated that the radiosensitizing effects of these modifiers could also be mediated through alterations in the oxidative stress besides energy limited inhibition of repair and recovery processes.

Drogas, inibidores y otras historias. De la quimioterapia a la toxicologia nutricional / Drugs, inhibitors and other stories. From cancer chemotherapy to nutritional toxicology

La designación como ponente de la XVIII Conferencia Annual "Karl Gaede", instituída por la Asociación Venezolana de Bioquímica y Biología Molecular, me brindó la oportunidad para emprender un viaje retrospectivo a través de algunos aspectos de la actividad de investigación realizada a lo largo de 25 años de dedicación al oficio de la bioquímica. Dicho derrotero se desplaza desde la quimioterapia del cáncer a la toxicología nutricional, siguiendo el elusivo hilo conductor del metabolismo, realidad subyacente bajo todo proceso biológico. El presente ensayo resume experiencias derivadas del abordaje de problemas metabólicos a través del uso de drogas, inhibidores y estimuladores que actúan sobre pasos enzimáticos específicos. Con estas herramientas del artesano metabólico es posible descorrer los velos que recubren al hilo conductor, para exponer las peculiaridades que lo caracterizan en el entorno de un problema particular y las semejanzas con los de otros que le dan continuidad en el amplio espectro del universo que nos atañe.

Morphological Changes of the Intestine of the Golden Hamster after Treatment with 6-Aminonicotinamide / 대한해부학회지

This study was untertaken to investigate the morphological changes of the intestine of the Golden Hamster after treatment with antimetabolites, 6-aminonicotinamide (6-AN), by light and electron microscopy. 6-AN induced a morphological change of the intestine, especially in the mucosa. Small and large vacuoles were created in the cytoplasm of enterocytes after 6-AN treatment, and these vacuoles were observed somewhat more often around the nucleus. Microvilli, nucleus and rER of the enterocytes were well preserved, but the mitochondria were showed a somewhat swollen appearance. Intercellular spaces between epithelial cells were enlarged, and the interdigitation of adjacent cytoplasmic processes formed by lateral cellular processes projecting from adjacent cells were observed with occasional appearance of blood cells in this space. Goblet cells and enteroendocrine cells were less affected by 6-AN than enterocytes. There were many lymphocytes, macrophages and degenerating cells in the lamina propria. Cytoplasmic inclusions with varying size and characteristics as well as cellular debrises of the degenerating cells were observed in the cytoplasm of macrophages. The myenteric plexus was changed by this antimetabolites. Ganglion cells did not change in their shape after treatment with 6-AN, but some structural changes were observed in the neuroglial cells and nerve fibers, and enlarged spaces between these structures were also observed. But no vacuoles were observed which were formed by degeneration of the intracellular organelles such as the mitochondria and the cisterna of the endoplasmic reticulum.