PMC full text:
Published online 2021 Sep 17. doi: 10.3390/ijms221810077
Table 1
In-vitro and in-vivo studies demonstrating mechanisms of arsenic neurotoxicity.
| Arsenic | Species | Exposure Duration | Pathological Mechanisms | Toxic Outcome | Ref. |
|---|---|---|---|---|---|
| Sodium arsenite | Rat | 4 months | Increased APP (amyloid precursor protein) and RAGE 9, also increased enzymatic activity of BACE1 (β-secretase). | Neurodegeneration disorders associated with amyloid accumulation. | [2] |
| Sodium arsenite | Rat | 1 month | Increased lipid peroxidation and decrease in nerve conduction velocity. myelin thickness, area, and perimeter of axons. | Impaired central nervous system. | [3] |
| Sodium arsenite | Rat | 9 h | Absence of neurofilament and fibroblast Proteins. | Altered cytoskeletal composition | [4] |
| Sodium arsenite | Rat | 28-days | Reduction in superoxide dismutase-2 and Catalase action in hippocampus, striatum and cortex. | Altered locomotor activity and grip strength. | [5] |
| Sodium arsenite | Rat | 4 months | Elevated oxidative stress, lipid peroxidation and reduced glutathione levels in brain mitochondria. | Increased oxidative stress and mitochondrial damage. | [39] |
| Sodium arsenite | Rat | 28-days | Increased oxidative stress. Decrease in superoxide dismutase-2 activity. | Increased apoptosis in brain cells. | [7] |
| Sodium arsenite | Rat | 10-weeks | Decrease in antioxidative defense mechanisms (GPx, GST, MnSOD, CAT and GR), enhanced LPO observed in the mitochondria at cerebral cortex, cerebellum and hippocampus. | Significant impact on behavioral functions like total locomotor activity, open field behavior, exploratory behavior and grip strength. | [136] |
| Sodium arsenite | Rat | 28-days | Increased oxidative stress in frontal cortex and hippocampus. Increased levels of Nrf2 and HO-1 proteins. | Demise of myelin sheath in neurons and imprecise cristae in the mitochondria both hippocampal and frontal cortex regions. Cholinergic deficits detected. | [137] |
| Sodium arsenite | Rat | 3 months | Biochemical and molecular modifications via inducing oxidative stress and dysfunction of mitochondria. | Mitochondrial decreasing complexes activity and functional impairment. | [31] |
| Sodium arsenite | Rat | 3 months | Reduced NR2A expression in the hippocampus. | Impaired memory. | [10] |
| Sodium arsenite | Rat | 3 months | mGluR5 mRNA and protein expression in hippocampus and cortex. | Learning and memory ability declined. | [11] |
| Sodium arsenite | Rat | 30 days | Lowered expression of NMDAR NR2B subunit and EAAC1 in the brain (hippocampus). | Spatial memory impairment. | [12] |
| Arsenic trioxide | Mice | 45 days | Significant raise in lipid peroxidation, glycogen in cerebral hemisphere and cerebellum. | Neurotoxic effects. | [13] |
| Arsenic trioxide | Mice | 60 days | Reduction of Sdha expression and activity in brain, mitochondrial respiratory chain genes downregulation. | Neurodegeneration disorders. | [14] |
| Arsenic trioxide | T98G and A172 cells | 6, 8 and 24 h | Aggregated mitochondria and MMP dissipation. | Induced apoptosis. | [138] |
| Arsenic trioxide | SY-5Y cells | 24, 48 and 72 h | Elevated intracellular calcium ions. | Increased occurrence of apoptosis and DNA damage. | [139] |
| Sodium arsenite | Primary astrocytes | 24 h | Decreased mitochondrial membrane permeability and decreased protein expression of GLT-1, GS, and GLAST. | Inhibit glutamate metabolism leading to neurotoxicity. | [67] |
| Arsenic trioxide | Rat neuronal cells | 8 h | Increased expression of calpain 1, cdk5, p25 levels. | Induced neuronal cell apoptosis. | [69] |
| Arsenic trioxide | Neuro-2a cells | 24 h | Oxidative stress damage decreased Nrf2 and thioredoxin expression. Mitochondrial dysfunction, PARP activation and caspase cascades, caspase-3 activity. | Neuronal cell death. | [70] |
| Sodium arsenite | Bergmann glial cells | 24 h | Increased EAAT1/GLAST activity and decrease in GLU transport. | Neuronal damage. | [71] |