Drug-induced toxicity is a key issue for public health because some side effects can be severe and life-threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug-induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug-induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug-induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01269898/document

Role of endoplasmic reticulum stress in drug‐induced toxicity

Arsenic is a naturally occurring element with a long history of toxicity. Sites of contamination are found worldwide as a result of both natural processes and anthropogenic activities. The broad scope of arsenic toxicity to humans and its unique interaction with the environment have led to extensive research into its physicochemical properties and toxic behavior in biological systems. The purpose of this review is to compile the results of recent studies concerning the metalloid and consider the chemical and physical properties of arsenic in the broad context of human toxicity and phytoremediation. Areas of focus include arsenic's mechanisms of human toxicity, interaction with plant systems, potential methods of remediation, and protocols for the determination of metals in experimentation. This assessment of the literature indicates that controlling contamination of water sources and plants through effective remediation and management is essential to successfully addressing the problems of arsenic toxicity and contamination.

Arsenic: A Review of the Element’s Toxicity, Plant Interactions, and Potential Methods of Remediation

Anticancer metal drugs and immunogenic cell death.

Arsenic (As) is a worldwide naturally occurring metalloid. Human chronic exposure to inorganic As compounds (iAs), which are at the top of hazardous substances (ATSDR, 2013), is associated with different diseases including cancer and non- cancerous diseases. The neurotoxic effects of iAs and its methylated metabolites have been demonstrated in exposed populations and experimental models. Impaired cognitive abilities have been described in children and adults chronically exposed to iAs through drinking water. Even though different association studies failed to demonstrate that As causes neurodegenerative diseases, several toxicity mechanisms of iAs parallel those mechanisms associated with neurodegeneration, including oxidative stress and inflammation, impaired protein degradation, autophagy, and intracellular accumulation, endoplasmic reticulum stress, and mitochondrial dysfunction. Additionally, different reports have shown that specifically in brain tissue, iAs and its metabolites induce hyper-phosphorylation of the tau protein and over-regulation of the amyloid precursor protein, impaired neurotransmitters synthesis and synaptic transmission, increased glutamate receptors activation, and decreased glutamate transporters expression. Interestingly, increased and sustained pro-inflammatory responses mediated by cytokines and related factors, seems to be the triggering factor for all of such cellular pathological effects. Therefore, this review proposes that iAs-associated cognitive impairment could be the result of the activation of pro-inflammatory responses in the brain tissue, which also may favor neurodegeneration or increase the risk for neurodegenerative diseases in exposed human populations.

Toxicity mechanisms of arsenic that are shared with neurodegenerative diseases and cognitive impairment: Role of oxidative stress and inflammatory responses

Potential use of the Pteris vittata arsenic hyperaccumulation-regulation network for phytoremediation.

Arsenic trioxide induces programmed cell death through stimulation of ER stress and inhibition of the ubiquitin–proteasome system in human sarcoma cells

Yin Chiu Tseng

Papers

Arsenic trioxide induces programmed cell death through stimulation of ER stress and inhibition of the ubiquitin–proteasome system in human sarcoma cells