The rapid transformation of triclosan in the liver reduces its effectiveness as inhibitor of hepatic energy metabolism.

Triclosan (5-chloro-2'-[2,4-dichlorophenoxi]-phenol) is a polychlorinated biphenolic antimicrobial, utilized as antiseptic and preservative in hygiene products and medical equipment. Triclosan causes mitochondrial dysfunction (uncoupling, inhibition of electron flow), as demonstrated in isolated rat liver mitochondria. These actions in the mitochondria could compromise energy-dependent metabolic fluxes in the liver. For this reason, the present work aimed at investigating how these effects on isolated mitochondria translate to the whole and intact hepatocyte. For accomplishing this, the isolated perfused rat liver was utilized, a system that preserves both microcirculation and the cell-to-cell interactions. In addition, the single-pass triclosan hepatic transformation was also evaluated by HPLC as well as the direct action of triclosan on gluconeogenic enzymes. The results revealed that triclosan decreased anabolic processes (e.g., gluconeogenesis) and increased catabolic processes (e.g., glycolysis, ammonia output) in the liver, generally with a complex pattern of concentration dependences. Unlike the effects on isolated mitochondria, which occur in the micromolar range, the effects on intact liver required the 10 to 10 M range. The most probable cause for this behavior is the very high single-pass transformation of triclosan, which was superior to 95% at the portal concentration of 100 μM. The concentration gradient along the sinusoidal bed is, thus, very pronounced and the response of the liver reflects mainly that of the periportal cells. The high rates of hepatic biotransformation may be a probable explanation for the low acute toxicity of triclosan upon oral ingestion.