Effect of tetracycline on the metabolism of [1-¹⁴C]oleate by the liver

The effects of tetracycline on the synthesis, outward transport, and accumulation of triglyglycerides from [1-¹⁴C]oleate were investigated using the isolated perfused rat liver. The effects of the antibiotic on production of CO₂, and ketone bodies were studied also. Tetracycline either was added to the medium perfusing livers from normal fed male rats, or alternatively, was administered to rats intravenously (pure tetracycline HCl, or Achromycin, 100 mg/kg body weight) 3 hr prior to removal of the livers for perfusion. The quantity ofoleate infused was sufficient to yield approximately half-maximal rates of output of triglycerides. Under these conditions, on the basis of the isotopic data, the hepatic accumulation of triglycerides derived from the exogenous sources (perfusate ¹⁴C free fatty acid) was balanced by a decrease in outward transport triglycerides, whether tetracycline was added directly to the medium perfusing the livers in vitro or was administered to the animals in vivo. Decreases in hepatic oxidation of oleate induced by tetracycline did not appear to be an important mechanism for induction of steatosis. These data suggest that the fatty liver resulting from intoxication by tetracycline results primarily from inhibition of outward transport of triglycerides.