Ruthenium Red Ameliorates Arsenic Trioxide Mediated Oxidative Stress and Behavioral Changes in Mice

Abstract

Groundwater poisoning by arsenic (As) is a serious global public health issue, especially in developing nations where access to clean drinking water is still scarce. Severe health problems, including as neurological disorders, vascular diseases, skin lesions, and cancer, have been linked to long-term exposure to arsenic through polluted water, food, inhalation, and skin contact. Hotspots for arsenic contamination include the Mekong Delta, the Terai region of Nepal, the Ganga–Brahmaputra–Meghna plains of Bangladesh and India, and numerous areas of China and Southeast Asia. Arsenic exposure may be a major cause of neurotoxicity, depression, anxiety, and cognitive impairment, according to growing epidemiological and experimental data. Oxidative stress, mitochondrial dysfunction, lipid peroxidation, compromised antioxidant defence systems, and disruptions in neurotransmitter modulation are among the underlying causes. Reactive oxygen species overproduction brought on by arsenic upsets cellular redox equilibrium, lowers glutathione and antioxidant enzyme activity, and encourages neuronal apoptosis and degeneration of the central nervous system. Ryanodine receptors (RyRs) and inositol trisphosphate receptors regulate dysregulation of intracellular calcium signalling, which exacerbates neuronal damage and impairs synaptic plasticity linked to learning and memory impairments. Because it can inhibit mitochondrial-dependent apoptotic signalling and restore calcium homeostasis, ruthenium red (RR), a specific antagonist of RyR-mediated calcium release, has become a promising neuroprotective drug. According to experimental results, RR may enhance cholinergic function in neurodegenerative diseases and lessen oxidative stress-induced neuronal damage. In order to combat arsenic-induced neurotoxicity and related neurological deficits, RyR inhibition may be used to target calcium dysregulation.