Antioxidative Therapy of Alcoholic Liver Injury by Amorphous Two-Dimensional Cobalt Hydroxide Nanocatalyst

The intake of excessive ethanol will activate an alternative ethanol metabolic pathway in the liver, resulting in the overproduction of reactive oxygen species (ROS), which further leads to alcoholic liver injury (ALI). Although several molecular antioxidants have been utilized in clinics for treating ALI, their efficacies are still less satisfactory. In this work, a nanocatalytic antioxidation therapeutic strategy is proposed for ALI treatment by constructing amorphous Co(OH)₂ nanosheets with catalytic antioxidative property. The bis(μ-hydroxo)Co^IICo^II dinuclear active sites of Co(OH)₂ nanosheets are capable of coordinating with hydrogen peroxide (H₂O₂) with significantly reduced thermodynamic barrier to form a dihydroxyl adduct bis(μ-hydroxo)Co^III(OH)Co^III(OH) favorable for catalytic H₂O₂ disproportionation, while amorphous and ultrathin structure further facilitates the reaction, resulting in a high catalytic efficiency (K_m=59.31 mM). Thanks to the inherent hepatic passive targeting ability of nanomaterials, the antioxidative nanosheets can accumulate in liver region efficiently after intravenous administration (35.5 % ID/g accumulation efficiency), enabling efficient catalytic antioxidation in the liver to mitigate hepatic oxidative stress, protect hepatocytes from apoptosis/ferroptosis. This study provides a new methodology of nanocatalytic antioxidation for treating ALI and other hepatic diseases related to oxidative stress.