Low-dose alcohol ameliorated homocysteine-induced anxiety-related behavior via attenuating oxidative stress in mice.

Recent studies showed that homocysteine (Hcy) levels were obviously elevated in patients with anxiety, furthermore, oxidative stress and inflammation were closely linked with Hcy-related damage. Despite alcohol exposure has differential effects on different forms of anxiety, the role of alcohol on anxiety-related behavior induced by high Hcy levels is still not entirely clear. The present study investigated the protective potential of low-dose alcohol against homocysteine-induced anxiety-related behavior and explored the possible underlying mechanisms. Mice were administered intragastrically with methionine (2.0 g/kg/day) or alcohol (0.6 g/kg/day). After 21 days of administration, the anxiety-related behavior was evaluated through open field (OF) and elevated plus maze (EPM) tests, and the variations of oxidative stress and inflammation levels were measured. The results of OF and EPM tests showed that the anxiety-related behavior in mice was prevented by alcohol treatment. Alcohol lowered the elevated serum Hcy levels and alleviated the damage of hippocampal tissues in hyperhomocysteinemia (HHcy) mice. Meanwhile, the superoxide dismutase (SOD) activity of the hippocampal tissues enhanced, and the malondialdehyde (MDA) concentration of the hippocampal tissues and the serum interleukin-1β (IL-1β) level decreased. In addition, after administering alcohol, the increase of superoxide dismutase 1 (SOD1), heme oxygenase 1 (HO-1) protein expression and the decrease of IL-1β protein expression were also detected in HHcy mice hippocampal tissues. Taken together, low-dose alcohol significantly ameliorated the Hcy-induced anxiety-related behavior in mice, which might be related to SOD1 and HO-1 upregulation and IL-1β downregulation.