Hepatotoxicity of Halothane Metabolites in Vivo and Inhibition of Fibroblast Growth in Vitro

Abstract

Following single intraperitoneal doses the halothane metabolites, trifluoroethanol (TFE) and trifluoroacetaldehyde hydrate (TFAIH), produced a marked dose-dependent accumulation of fat in mouse liver, the maximal effect occuring at about 24 hours after administration. Slight fatty changes already occurred with non-lethal doses, but repeated administration did not, however, cause necrosis of the liver cells. Electron microscopy suggested that part of the fat was composed of phospholipids, which are known to accumulate during energy loss. The glycogen granules almost completely disappeared in the liver, this being also confirmed by chemical determination. Trifluoroacetic acid (TFAA) not only caused slight fat accumulation, but also an increase in liver glycogen. In human fibroblast cell cultures TFAIH, even in small concentrations, and TFAA in high concentrations, inhibited cell growth. TFE did not affect the growth of the fibroblasts, probably because no enzymatic system is available in these cells to metabolize TFE to the toxic aldehyde. Two mechanisms may be responsible for the hepatotoxicity of TFE and TFAIH: a) formation of phospholipids due to energy requirement and b) accumulation of liver triglycerides due to blocking of e. g. transport enzymes.

Variability of Microcystin-LR Standards Available from Seven Commercial Vendors

“…injection of 1000 mg/kg NaTFA 24 h prior demonstrated mild liver changes described as a slight accumulation of lipids and glycogen. Serum chemistry parameters were not performed in this study [ 55 ]. Since the exact amount of TFA in the present study was not determined, it is difficult to compare, but given the large exposure in the Blake and Rosenberg studies and lack of toxicity in Vendor A, any contribution from the TFA in the MCLR seems minor.…”