Arsenic induced alterations in erythrocyte redox balance, morphology, bioenergetics associated with GLUT1 degradation and hexokinase inhibition: Melatonin-mediated cytoprotection-a mechanistic insight.

Priority environmental toxicant arsenic directly enters to the bloodstream through contaminated water or foodstuffs. Erythrocytes, being the most abundant and vulnerable blood cell therefore demand detailed assessment of the hazardous metalloid-driven impacts. This study investigates a mechanistic basis of arsenic-induced impairments in goat erythrocytes and further evaluates protective efficacy of melatonin against the alterations. In-vitro exposure of erythrocytes to 100 μM arsenic causes ROS accumulation and redox imbalance resulting morphological deformation and critical membrane proteins loss. Degradation of GLUT1, reduced intracellular glucose availability, binding affinity toward glucose, suppressed metabolic enzyme activities and uncompetitive inhibition induced destabilization of hexokinase secondary structure by arsenic collectively underlines a mechanism of the toxic metalloid-driven erythrocyte dysfunctions and energetic failure. However, co-incubation of erythrocytes with 100 μM melatonin significantly ameliorates the oxidative imbalances and preserves RBC morphology through its antioxidant and radical-scavenging efficacy. Melatonin preventing GLUT1 degradation and preserving hexokinase conformation supports erythrocyte bioenergetics as evidenced by enhanced metabolic enzyme activities and intracellular ATP levels. Alongside, direct binding of melatonin with arsenic through its chelation capability highlight the indolamine as a promising candidate to mitigate arsenic-induced cytotoxicity either through its pharmacological administration or through the inclusion of melatonin-rich foods in daily diet to benefit humankind.