Dr. JUAN ARCADIO MOLINA-GUARNEROS

Coumarin has antitumour effects in vivo and cytostatic effects in vitro. Its half-life in humans is short (1-1.5 h) and the monohydroxylated biotransformation products have significantly longer half-lives. One or several of these products may thus be responsible for the antitumoral effects. We have assayed the in vitro cytostatic activity of five monohydroxylated coumarins (3-, 4-, 6-, 7- and 8-monohydroxycoumarin), their acetates and methyl-ethers. Murine melanoma cells (cell line B16-F10) and murine fibroblasts (B82) were exposed to the test compounds at concentrations between 10 and 160 microg/ml. The cytostatic effects were estimated by reduction of the tetrazolium dye MTT. In the melanoma cells, some of the compounds inhibited growth after exposure for 1 day. In contrast, coumarin inhibited growth to a smaller extent, and only after exposure for 3 days. The most active compounds (3-acetoxycoumarin, 4-methoxycoumarin and 6-hydroxycoumarin), as well as coumarin, were also assayed in murine fibroblasts. The cytostatic effects of 4-methoxycoumarin and 6-hydroxycoumarin were less pronounced in fibroblasts than in melanoma cells. Our observations suggest that these compounds may have a greater therapeutic margin.

4 April 2014 in International Journal of Molecular Sciences

Journal Article

Cystatin C Has a Dual Role in Post-Traumatic Brain Injury Recovery

Ruben Gonzalez-Rivera

Luz Navarro

Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles) increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles) decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.

10 September 2008 in Journal of Andrology

Journal Article

Activation of Protein Kinase A Stimulates the Progesterone‐Induced Calcium Influx in Human Sperm Exposed to the Phosphodiesterase Inhibitor Papaverine

Víctor Torres‐Flores

Yadira Libertad Hernández‐Rueda

Paloma Del Neri‐Vidaurri

Carmen Francisco Jiménez‐Trejo

Víctor Calderón‐Salinas

Marco T. González‐Martínez

Progesterone induces a fast transient calcium influx in human sperm though the activation of nongenomic receptors. During sperm capacitation, a complex process required for sperm to be able to fertilize the egg, the calcium influx induced by progesterone is enhanced. Sperm capacitation is mediated by an increase in cAMP content and subsequent protein kinase A (PKA) activation. In this work, we examined the effect of increasing intracellular cAMP on the calcium influx induced by progesterone in noncapacitated human sperm. To do this, sperm were exposed to the phosphodiesterase inhibitor papaverine for 5 minutes, a treatment that increased both the cAMP content and the PKA activity several‐fold. The calcium influx induced by progesterone was increased by papaverine to levels close to those found in capacitated sperm. This effect was partially inhibited by H89 (48%) and by genistein (41%), and the sum of both inhibitors reduced the stimulating effect of papaverine by 89%. The inhibitory effect of genistein on the progesterone‐induced calcium influx could be related to its capability to inhibit the papaverine‐stimulated increase in cAMP content and PKA activity. The results presented here suggest that the calcium influx induced by progesterone is up‐regulated by the PKA activity.

About Me

Medical Doctor (1981), Master of Science, specialized in Cellular Biology (1995), Philosophy Doctor in Biomedical Science (2006), UNAM. Affiliation: Pharmacology Department School of Medicine , National Autonomous University of Mexico , Mexico. Research and Academic Experience: Tenure Lecturer of Pharmacology, 35 years of of academic career starting as Assistant Professor, then Associated Professor. Presently, Tenured Lecturer at the Pharmacology Department (FacMed, UNAM). Medical undergraduate and postgraduate Professor . Thesis Director of multiple MSc and PhD projects. Currently working in the field of DMT2 clinical pharmacology and pharmacovigilance. Previously involved in the fields of coumarin pre-clinical pharmacology and its cell line metabolites in human lung cancer, as well as in vitro and in vivo immunopharmacology. Research Area: Diabetes Mellitus Type 2 pharmacogenetics, Clinical Pharmacology, Pharmacoepidemiology. Number of Published papers: 30 (PUBMED;) of them in journals indexed by Journal Citation Reports). Any other remarkable point(s): Head Researcher, Immunopharmacology laboratory, Pharmacology Department, School of Medicine, National Autonomous University of Mexico UNAM. (2005-present ). National Researcher Level II of the National Science and Technology Council (Mexico) 2007- 2023, Academic Tutor in postgraduate programmes of Biological, Biomedical, and Medical Sciences. Tenure Fellowship, National Academy of Medicine, Mexico.

Dr. JUAN ARCADIO MOLINA-GUARNEROS

Dr. JUAN ARCADIO MOLINA-GUARNEROS

Research Focus & Metrics

Academic Career Length

Publication Type Breakdown

Representative Publications

About Me