Observations placeholder
Arsenic and drinking water, chelation therapy
Identifier
017785
Type of Spiritual Experience
Background
Monoisoamyl DMSA (MiADMSA), is a lipophilic chelating agent . Tests have been carried out using MiADMSA alone on rats with some success, although the long term effects are not known
"Rats were exposed to arsenic (25 ppm) for 6 months and later received MiADMSA (50 or 100 mg/kg) orally and via i.p. route for 5 days. Oxidative stress parameters and arsenic levels in soft tissues, liver function test and histopathology of liver and kidney were performed. Plasma kinetic of MiADMSA (plasma-free drug and total drug) at 50 and 100 mg/kg p.o. was carried out. Arsenic exposure resulted in significant oxidative stress and hepatotoxicity. MiADMSA at 50 mg/kg dose administered orally provided about 45% and 75% protection against oxidative stress and in lowering body arsenic burden, respectively, against 25% and 40% via i.p. route. Pharmacokinetic analysis supported prolonged availability of the drug through oral administration. Collectively, these findings led us to conclude that oral administration of MiADMSA was more effective than intraperitoneal administration and that the minimum effective dose with least side effects was 50 mg/kg. PMID: 22117535"
A description of the experience
Neurotoxicology. 2013 Mar;35:137-45. doi: 10.1016/j.neuro.2013.01.006. Epub 2013 Jan 29.
Arsenic induced neuronal apoptosis in guinea pigs is Ca2+ dependent and abrogated by chelation therapy: role of voltage gated calcium channels.
Pachauri V1, Mehta A, Mishra D, Flora SJ.
- 1Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
Abstract
Arsenic contaminated drinking water has affected more than 200 million people globally.
Chronic arsenicism has also been associated with numerous neurological diseases.
One of the prime mechanisms postulated for arsenic toxicity is reactive oxygen species (ROS) mediated oxidative stress. In this study, we explored the kinetic relationship of ROS with calcium and attempted to dissect the calcium ion channels responsible for calcium imbalance after arsenic exposure. We also explored if mono- or combinational chelation therapy prevents arsenic-induced (25ppm in drinking water for 4 months) neuronal apoptosis in a guinea pig animal model.
Results indicate that chronic arsenic exposure caused a significant increase in ROS followed by NO and calcium influx. This calcium influx is mainly dependent on L-type voltage gated channels that disrupt mitochondrial membrane potential, increase bax/bcl2 levels and caspase 3 activity leading to apoptosis. Interestingly, blocking of ROS could completely reduce calcium influx whereas calcium blockage partially reduced ROS increase.
While in general mono- and combinational chelation therapies were effective in reversing arsenic induced alteration, combinational therapy of DMSA and MiADMSA was most effective. Our results provide evidence for the role of L-type calcium channels in regulating arsenic-induced calcium influx and DMSA+MiADMSA combinational therapy may be a better protocol than monotherapy in mitigating chronic arsenicosis.
Copyright © 2013 Elsevier Inc. All rights reserved.
PMID: 23376091