Peroxisomes are involved in the swift increase in alcohol metabolism

The purpose of this study was to determine whether catalase-dependent alcoh ol metabolism is activated by alcohol (i.e., swift increase in alcohol meta bolism). When ethanol or the selective substrate for catalase, methanol, wa s given (5.0 g/kg) in vivo 2 to 3 h before liver perfusion, methanol and ox ygen metabolism were increased significantly. This increase was blocked whe n the specific Kupffer cell toxicant GdCl3 was administered 24 h before per fusion. These data support the hypothesis that catalase-dependent alcohol m etabolism is activated by acute alcohol and that Kupffer cells are involved . Ethanol treatment in vivo increased ketogenesis from endogenous fatty aci ds nearly 3-fold and increased plasma triglycerides and hepatic acyl CoA sy nthetase activity; all increases were blocked by GdCl3,. These findings sup port the hypothesis that ethanol increases H2O2 supply for catalase-depende nt alcohol metabolism by increasing fatty acid supply, infusion of oleate s timulated oxygen uptake 1.5-fold and methanol metabolism 4-fold, but these parameters were not altered by GdCl3. Moreover, the effects of ethanol trea tment were blocked by the cyclooxygenase inhibitor indomethacin, and prosta glandin E-2 (PGE(2)) was increased more than 200% in media from cultured Ku pffer cells from rats treated with ethanol in vivo. Furthermore, lipoprotei n lipase activity in retroperitoneal fat pads, which is known to be inhibit ed by PGE(2), was reduced 70% by ethanol. These data are consistent with th e hypothesis that Kupffer cells play a key role in activation of catalase-d ependent alcohol metabolism, most likely by producing mediators (e.g., PGE( 2)) that inhibit lipoprotein lipase, increase the supply of fatty acids to the liver, and increase generation of H2O2 via peroxisomal beta-oxidation.