Enrique Rosenbaum - Academia.edu (original) (raw)

Papers by Enrique Rosenbaum

Toxicology in Vitro, Apr 1, 2016

The placenta and trophoblasts express several B-esterases. This family includes acethylcholineste... more The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 0.33 and 0.26mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4h treatment while Cp showed the highest inhibition profile at 24h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy.

Toxicology in Vitro, 2016

Biochemical Pharmacology, Feb 1, 1991

Newly fertilized Bufo arenarum Hensel embryos were exposed continuously or for a brief period (72... more Newly fertilized Bufo arenarum Hensel embryos were exposed continuously or for a brief period (72-120hr) to malathion (44ppm) and then resuspended in amphibian Ringer's solution. Continuous exposure depressed acetylcholinesterase (EC 3.1.1.7), butyrylcholinesterase (EC 3.1.1.8) and carboxylesterase (EC 3.1.1.1) activities. The activities of the three enzymes in embryos treated for 72 hr recovered after a delay of 24 hr, but these enzymes showed different rates of recovery in embryos treated for 120 hr. Acrylamide disc electrophoresis showed several bands of esterase activity in control embryos. Continuous exposure to malathion abolished all esterase activity within 48 hr, but if the exposure continued new bands of esterase activity appeared at 120 hr of exposure. The zymograms of embryos exposed for 72 or 120 hr to malathion and then transferred to uncontaminated medium for 120 hr were similar to that of control embryos.

Amphibians are good bioindicators of environmental pollution due to their susceptibility to chemi... more Amphibians are good bioindicators of environmental pollution due to their susceptibility to chemicals during their freshwater cycles. The effects of environmental pollution, together with changes in human activity and climate, have contributed to the reduction in the amphibian population over recent decades. However, toxicological research on amphibians has been rather scarce compared with that on other vertebrates. In this article we review the biochemical alterations underlying xenobiotic action and/or the detoxifying responses described for anuran species, with the aim of establishing possible biomarkers of effect. During the embryonic development of anurans, morphological and behavioural alterations are the effects most frequently cited in connection with chemical exposures. However, such biomarkers have a low sensitivity and are unspecific compared with biochemical alterations. Some primary pesticide targets, in particular cholinesterases for organophosphates and carbamates, ha...

Toxicology Letters, 1998

... The effect of pesticides on amphibians. Authors: Venturino A.; de Schroeder TMF; Rosenbaum E.... more ... The effect of pesticides on amphibians. Authors: Venturino A.; de Schroeder TMF; Rosenbaum E.; de Castro AC; Anguiano OL; Gauna L.; de D'Angelo AMP. ... You may be required to register, activate a subscription or purchase the article before you can obtain the full text. ... list. ...

Journal of Biological Systems, 2002

Polyamines act as dual modulators on electric eel acetylcholinesterase, modifying both the appare... more Polyamines act as dual modulators on electric eel acetylcholinesterase, modifying both the apparent Km and Ki, depending on substrate levels. A kinetic model was developed to explain the results, based on two-step catalysis, a peripheral site for substrate inhibition apart from the catalytic site, and one binding site for polyamine. This model presented the best fittings to data, when compared with a simpler one considering one catalytic step. A fitting equation built up with sixteen independent parameters let us calculate the kinetic constants. In this way, we were able to solve the parameter identifiability problem arising from model uncertainty when only substrate was used in acetylcholinesterase kinetics. Besides, fitting parameters directly provide information about the binding constants of the different complexes, the modulatory strength of substrate and polyamines, and the effect on the standard activation free energy for acetylcholinesterase. Substrate inhibition operates ma...

Journal of Biological Systems, 1999

Acetylcholinesterase (E.C. 3.1.1.7) is a typical hydrolase showing substrate inhibition. Classica... more Acetylcholinesterase (E.C. 3.1.1.7) is a typical hydrolase showing substrate inhibition. Classical works stated a two-step kinetics for the catalytic mechanism. We analyse here a full interacting model for the substrate bound to an inhibitory site different to the catalytic one, in agreement with current tridimensional data. A mixed model derived from equilibrium-steady state analysis fits fairly well to experimental data. We conclude that both catalytic steps are susceptible of partial inhibition, with 15% of remaining activity for substrate saturated enzyme. Indeed, substrate inhibition would be preferentially exerted on one of the catalytic steps, leading to particular cases which fit to data as well. The parametric identity among the mathematical expressions from restricted models disables identifiability of kinetic constants solely by fitting to data. Thus, additional information is required from other experimental approaches. Based on the cited closeness between both rate cons...

Journal of Biochemical and Molecular Toxicology, 2008

Amphibians may be critically challenged by aquatic contaminants during their embryonic developmen... more Amphibians may be critically challenged by aquatic contaminants during their embryonic development. Many classes of compounds, including organophosphorus pesticides, are able to cause oxidative stress that affects the delicate cellular redox balance regulating tissue modeling. We determined the progression of antioxidant defenses during the embryonic development of the South American common toad, Bufo arenarum. Superoxide dismutase (SOD) and catalase (CAT) activities were high in the unfertilized eggs, and remained constant during the first stages of development. SOD showed a significant increase when the gills were completely active and opercular folds began to form. Reductase (GR) activity was low in the oocytes and increased significantly when gills and mouth were entirely developed and the embryos presented a higher exposure to pro‐oxidant conditions suggesting an environmental control. Reduced glutathione (GSH) content was also initially low, and rose continuously pointing out ...

Environmental Toxicology and Chemistry, 2012

The authors evaluated biomarker responses in caged larvae of the amphibian Rhinella arenarum in w... more The authors evaluated biomarker responses in caged larvae of the amphibian Rhinella arenarum in water channels during fruit production season and compared them with those elicited by a transient exposure to azinphos methyl (AzM) (0.02–2 mg/L; 4 h), the main pesticide applied in the Alto Valle region, Patagonia, Argentina, taking into account the maximum environmental concentration detected in superficial water (22.5 µg/L). The traditional biomarkers of organophosphate exposure, acetylcholinesterase (AChE) and carboxylesterase, were inhibited in tadpoles after one week of exposure in channels potentially receiving pesticide drift, whereas the antioxidant glutathione (GSH) and the detoxifying activity of GSH S‐transferase (GST) were induced. In a two‐week monitoring study, AChE activity was induced in larvae exposed at the agricultural site, and carboxylesterase showed an inhibition followed by return to control values, suggesting an exposure–recovery episode. Antioxidant glutathione ...

Biochemical Pharmacology, 1991

Archives of Environmental Contamination and Toxicology, 1988

The exposure of newly fertilized amphibian embryos to malathion (44 mg/L) produces 67% mortality ... more The exposure of newly fertilized amphibian embryos to malathion (44 mg/L) produces 67% mortality on tl~e fifth day of exposure. Clinical signs of intoxication are evident on the fourth day. A variety of biochemical parameters, such as enzyme activity, lipid and protein content, was examined in control and malathion-treated embryos. The activity of acetyl, butyrylcholinesterase and aliesterase are quickly inhibited. An interference with cellular protein synthesis and redistribution is possible. A slight increase in total phospholipids is evident after 24 hr of exposure.