Time-dependent post-exposure self-recovery rescues arsenic-induced behavioral and biochemical alterations in mice

Chronic arsenic (As)-exposure leads to behavioral and biochemical changes both in humans and laboratory animals. However, post-exposure self-recovery after prolonged As-exposure remains unclear. This study evaluated the effects of As-exposure via drinking water (5 mg/kg body-weight/day) for 60 days and post-exposure self-recovery at 30-, 45-, and 60-days on behavioral and biochemical alterations in a mouse model. As-exposure mice exhibited augmented anxiety, impaired memory, and decreased motor coordination compared to controls. Furthermore, diminished cholinesterase and antioxidant environment, increased inflammation, and elevated Fe²⁺ levels were observed in brains of As-exposed mice. However, after stopping drinking As-contaminated water, recovery groups showed less anxiety, improved memory, and motor coordination. Moreover, levels of Nrf2, HO-1, and GSH, and activities of SOD, AChE, and BChE were significantly increased in brains of 45- and 60-days recovery groups compared to As-exposed group. Besides, remarkably reduced Fe²⁺ and MDA levels, concurrent with increased GPx4 activities in brains of the 45- and 60-days recovery groups, indicate attenuation of ferroptosis. Additionally, 45- and 60-days recovery groups showed decreased levels of IL-1β and IL-6, while increased IL-10 levels indicated reduced inflammation. These results suggest that stopping As-intake facilitates the attenuation of oxidative stress-mediated anxiety, cognitive, and motor coordination impairment in As-exposed mice.