THE ROLE OF ESTERASE INHIBITION IN TETRAETHYLPYROPHOSPHATE POISONING IN THE HOUSEFLY, MUSCA DOMESTICA L.

1960 ◽  
Vol 38 (1) ◽  
pp. 1417-1430 ◽  
Author(s):  
D. Stegwee

The effect of tetraethylpyrophosphate (TEPP) was studied on the in vivo activity of different esterases in the housefly. TEPP was found to cause inhibition of the acetylcholinesterase and of the ali-esterase which hydrolyzes ethylbutyrate. The latter esterase could be selectively inhibited in vivo by treating the flies with tri-o-cresylphosphate (TOCP). Typical symptoms of organophosphorus poisoning developed only after TEPP when acetylcholinesterase was inhibited. Inhibition of this enzyme coincided with a rise of the level of acetylcholine in the insects. Treatment with TOCP caused a lowering of the level of acetylcholine. The insects became less sensitive to subsequent treatment with TEPP and in this case showed a lesser degree of accumulation of acetylcholine. The importance of acetylcholinesterase and ali-esterase in TEPP poisoning is discussed. It is concluded that the major biochemical lesion effected was the inhibition of acetylcholinesterase. Inhibition of the ali-esterase was not directly related to the toxic action of TEPP, although possibly it led to interference with the accumulation of acetylcholine resulting from the acetylcholinesterase inhibition.

1960 ◽  
Vol 38 (12) ◽  
pp. 1417-1430 ◽  
Author(s):  
D. Stegwee

The effect of tetraethylpyrophosphate (TEPP) was studied on the in vivo activity of different esterases in the housefly. TEPP was found to cause inhibition of the acetylcholinesterase and of the ali-esterase which hydrolyzes ethylbutyrate. The latter esterase could be selectively inhibited in vivo by treating the flies with tri-o-cresylphosphate (TOCP). Typical symptoms of organophosphorus poisoning developed only after TEPP when acetylcholinesterase was inhibited. Inhibition of this enzyme coincided with a rise of the level of acetylcholine in the insects. Treatment with TOCP caused a lowering of the level of acetylcholine. The insects became less sensitive to subsequent treatment with TEPP and in this case showed a lesser degree of accumulation of acetylcholine. The importance of acetylcholinesterase and ali-esterase in TEPP poisoning is discussed. It is concluded that the major biochemical lesion effected was the inhibition of acetylcholinesterase. Inhibition of the ali-esterase was not directly related to the toxic action of TEPP, although possibly it led to interference with the accumulation of acetylcholine resulting from the acetylcholinesterase inhibition.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Melissa Faria ◽  
Natàlia Garcia-Reyero ◽  
Francesc Padrós ◽  
Patrick J. Babin ◽  
David Sebastián ◽  
...  

Abstract Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.


Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.


2020 ◽  
Vol 64 (2) ◽  
pp. 251-261
Author(s):  
Jessica E. Fellmeth ◽  
Kim S. McKim

Abstract While many of the proteins involved in the mitotic centromere and kinetochore are conserved in meiosis, they often gain a novel function due to the unique needs of homolog segregation during meiosis I (MI). CENP-C is a critical component of the centromere for kinetochore assembly in mitosis. Recent work, however, has highlighted the unique features of meiotic CENP-C. Centromere establishment and stability require CENP-C loading at the centromere for CENP-A function. Pre-meiotic loading of proteins necessary for homolog recombination as well as cohesion also rely on CENP-C, as do the main scaffolding components of the kinetochore. Much of this work relies on new technologies that enable in vivo analysis of meiosis like never before. Here, we strive to highlight the unique role of this highly conserved centromere protein that loads on to centromeres prior to M-phase onset, but continues to perform critical functions through chromosome segregation. CENP-C is not merely a structural link between the centromere and the kinetochore, but also a functional one joining the processes of early prophase homolog synapsis to late metaphase kinetochore assembly and signaling.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.


2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap

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