Lamivudine Remedies Alcoholism By Activating Acetaldehyde Dehydrogenase In Mice

With the continuous expansion of global drinking population and alcohol consumption,acute alcoholism has become one of the main hazards caused by the intake of alcoholic beverages,which poses a serious threat to global public health.The huge alcohol consumption market has given birth to a variety of anti-alcohol products.However,the products on the market at present are difficult to rapidly promote the metabolism of acetaldehyde.Therefore,there is an urgent need for anti-alcohol products with high efficiency to speed up acetaldehyde metabolism.In the current work,we first screened clinical drugs for anti-alcohol stress activity by constructing an alcohol pressure cell model and found that lamivudine shows potent anti-alcohol stress activity at the cellular level.Secondly,we suspected that acetaldehyde dehydrogenase Ⅱ（Acetaldehyde dehydrogenase Ⅱ,ALDH2）is a direct target of lamivudine.By constructing the DH5α/pET-28a-ALDH2 strain,ALDH2 was expressed and purified to directly detect the effect of lamivudine on ALDH2 in vitro,and the results indicated that lamivudine significantly activates ALDH2 activity.Finally,we found that lamivudine also protects mice from acute alcoholism,including remarkably relief of symptoms post drinking,such as prolonging alcohol tolerance time and shortening sobering time,and reduction of alcohol-induced mortality.Our results supported that lamivudine reduces serum alcohol concentration dramatically,and potently activates acetaldehyde dehydrogenase（Acetaldehyde dehydrogenase,ALDH）to accelerate the conversion of acetaldehyde to acetic acid,which is finally metabolized by tricarboxylic acid cycle to be CO₂ and H₂O.This work will provide new strategies for the prevention and treatment of acute alcoholism.