Kinetic properties of Streptomyces canarius L- Glutaminase and its anticancer efficiency

Abstract L-glutaminase was produced by Streptomyces canarius FR (KC460654) with an apparent molecular mass of 44 kDa. It has 17.9 purification fold with a final specific activity 132.2 U/mg proteins and 28% yield recovery. The purified L-glutaminase showed a maximal activity against L-glutamine when incubated at pH 8.0 at 40 °C for 30 min. It maintained its stability at wide range of pH from 5.0 11.0 and thermal stable up to 60 °C with Tm value 57.5 °C. It has high affinity and catalytic activity for L-glutamine (Km 0.129 mM, Vmax 2.02 U/mg/min), followed by L-asparagine and L-aspartic acid. In vivo, L-glutaminase showed no observed changes in liver; kidney functions; hematological parameters and slight effect on RBCs and level of platelets after 10 days of rabbit's injection. The anticancer activity of L-glutaminase was also tested against five types of human cancer cell lines using MTT assay in vitro. L-glutaminase has a significant efficiency against Hep-G2 cell (IC50, 6.8 μg/mL) and HeLa cells (IC50, 8.3 μg/mL), while the growth of MCF-7 cells was not affected. L-glutaminase has a moderate cytotoxic effect against HCT-116 cell (IC50, 64.7 μg/mL) and RAW 264.7 cell (IC50, 59.3 μg/mL).

Toxicity of sucralose in humans: a review / Toxicidad de la sucralosa en humanos: una revisión

Sucralose is a non-nutritive artificial sweetener, 600 times sweeter than sucrose, and is very stable at high temperatures, among other characteristics. It was approved by the FDA, in 1999, to be utilized in foods, beverages, pharmaceutical products, diets and vitamin supplements. Studies suggest a diffusion, through the placental barrier, of small doses of sucralose and its metabolites. Its hydrolysis products (4-CG e 1,6-DCF) are more rapidly absorbed than sucralose: 4-CG is excreted intact in the urine, and 1,6-DCF undergoes reduction with elimination by the urine or rapid conjugation with glutathione. Various organs can be affected by ingestión of high doses of sucralose. As a result of the rise in global consumption of sweeteners and light- or diet-type products, studies are necessary to evaluate the action of this substance in the human species. The present study aims to accomplish a review of the literature that involves its indications of use, pharmacodynamics as well as the carcinogenic, teratogenic, neurotoxic, and nephrotoxic potentials of sucralose.

La sucralosa es un edulcorante artificial no nutritivo, 600 veces más dulce que la sacarosa, y es muy estable a altas temperaturas, entre otras características. Fue aprobado por la FDA, en 1999, para ser utilizada en los alimentos, bebidas, productos farmacéuticos, dietéticos y suplementos vitamínicos. Los estudios sugieren una difusión a través de la barrera placentaria, de pequeñas dosis de la sucralosa y sus metabolitos. Sus productos de hidrólisis (4-CG e 1,6-DCF) se absorben más rápidamente que la sucralosa: 4-CG se excreta intacta en la orina, y el 1,6-DCF sufre reducción con la eliminación por la orina o la rápida conjugación con glutatión. Diversos órganos pueden verse afectados por la ingestión de altas dosis de sucralosa. Como resultado del aumento en el consumo mundial de los edulcorantes y productos de tipo light o diet, son necesarias investigaciones para evaluar la acción de esta sustancia en la especie humana. El presente estudio tiene como objetivo realizar una revisión de la literatura que trata de las indicaciones de uso, la farmacodinamia, así como los potencialidades cancerígenas, teratogénicas, neurotóxicas y nefrotóxicas de la sucralosa.