Trifluoroacetylated proteins in liver and plasma of guinea pigs treated with HCFC-123 and halothane.
Trifluoroacetylated (TFA)-protein adducts were investigated by immunoblotting in liver and plasma of guinea pigs treated with the hepatotoxic anaesthetic halothane or the chlorofluorocarbon replacement 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123). Male outbred Hartley guinea pigs (320-400 g) were administered HCFC-123 (1, 5, 10 and 15 mmol/kg b.w.) or halothane (positive control, 10 mmol/kg b.w.) i.p. in corn oil. Blood and liver samples were collected 24 h after administration of HCFC-123 or halothane. Immunoreactive bands were demonstrated in liver microsomes at all HCFC-123 and halothane concentrations, and in plasma of animals treated with 10 and 15 mmol/kg b.w. HCFC-123 and 10 mmol/kg b.w. halothane, while no alteration of microsomal P450 content or monooxygenase activities markers of the P450 2A, 2E1 and 2B isoforms was observed. Instead, when HCFC-123 was administered at doses of 1 and 5 mmol/kg b.w., the 2E1-dependent p-nitrophenol hydroxylase activity was enhanced. The presence of TFA-proteins in plasma was always associated with hepatic damage. However, mild liver damage in some animals treated with 1 or 5 mmol/kg b.w. HCFC-123 was not associated with the presence of TFA-proteins in plasma. This indicates a lower threshold dose for the appearance of TFA-proteins or damage in the liver (1 mmol/kg b.w.) than for the presence of TFA-proteins in plasma (10 mmol/kg b.w.), thus suggesting that the presence of TFA-proteins in plasma may be the result of liver damage.
Bortolato
Silvia
S
Department of Environmental Medicine and Public Health, University of Padua, Via Giustiniani 2, 35128 Padova, Italy.
Zanovello
Alberta
A
Rugge
Massimo
M
Brotto
Maurizio
M
Marini
Sandra
S
Gervasi
Pier Giovanni
PG
Manno
Maurizio
M
D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001391:Azo Compounds; D015415:Biomarkers; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology; D017402:Chlorofluorocarbons / Q000494:pharmacology*; D064227:Chlorofluorocarbons, Ethane; D004396:Coloring Agents; D003402:Creatine Kinase / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011506:Proteins / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000097:blood / Q000737:chemistry*
D018685:Anesthetics, Inhalation; D001391:Azo Compounds; D015415:Biomarkers; D017402:Chlorofluorocarbons; D064227:Chlorofluorocarbons, Ethane; D004396:Coloring Agents; D011506:Proteins; C067411:2,2-dichloro-1,1,1-trifluoroethane; D003577:Cytochrome P-450 Enzyme System; D014269:Trifluoroacetic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; C032756:ponceau S; D006221:Halothane