Effects of arsenic on neuronal intracellular signal pathways with special regard to estrogen-mediated processes

Abstract

Arsenic is found in many geological formations and contaminated drinking water, posing a great global threat. Besides several beneficial effects on tumour degeneration, therapy of promyelocytic leukaemia was discovered. Arsenic is proven to cause a higher incidence of benign and malignant tumours when being exposed to arsenic in utero. Furthermore arsenic is connected with interference in DNA synthesis and repair, as well as with lipid and protein peroxidation causing oxidative stress. It also destructs vital functions of the body in humans and animals, such as inducing mitochondrial swelling and oedema of synapses. Acute arsenic intoxication often results in gastrointestinal symptoms, skin lesions and shock, ultimately resulting in the death of the patient. One of arsenic’s main attributes is invading the neurological system, causing a degeneration of neurons. It further results in a decreased intelligence quotient (IQ), peripheral paralysis, cognitive dysfunction, and alterations in locomotion and memory loss. There has been a correlation between arsenic intoxication and depression. Arsenic acts also as a great endocrine disruptor (ED) causing disturbances in regulations mediated by estrogen and other steroids. It is assumed that the estrogen receptor (ER) is very sensitive to arsenic. Low doses of arsenic have been proven to suppress certain hormones whilst enhancing others. Contrary to its toxicity, arsenic also has a positive chemotherapeutic impact on estrogen receptor alpha (ERα).