ABSTRACT
Objective To evaluate the blood clearance,tissue uptake and distribution as well as safety of high dose-40 mg intravenous fish oil/'medium chain triglycerides (FO/MCT:2 ∶ 8,wt/wt) lipid emulsions iu mice by measuriug the contents of triglycerides (TG) and free fatty acids (FFA) level in blood.Methods FO/MCT emulsions were radiolabeled with nondegradable [3H] cholesteryl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection.For high dose,TG was 40 mg,100 times of low dose.Blood samples were obtained within 25 min to analyze TG and FFA concentrations;extracted organs were used to measure the tissue distribution of lipid emulsions.Results No animal in either group died,and no fat overload syndrome evidence was found after high dose injection.Compared with low dose,high dose injection increased the plasma TG and FFA concentrations rapidly;the emulsions were cleared significantly slower during 25 min after administration in mice;blood has a higher uptake ratio in organs,but heart has a lower one;there was no significant difference in liver and lung uptake ratio between the two groups.Conclusions High dose injection of FO/MCT is not fatal in mice.The animals only experience hypertriglyceridemia and high level of free fatty acids during a significant slower blood clearance period compared to low dose.Although blood clearance is slower,the blood uptake rate increases for further metabolism and clearance.Heart and lung functions are not affected as a lower cardiac and pulmonary uptake;blood uptakes more emulsions to further metabolize.FO/MCT may not induce fat overload syndrome in mice when administered with a super high dose.
ABSTRACT
The chemical structures of mequindox related metabolites in chicken plasma had been investigated using high performance liquid chromatography combined with linear ion trap quadrupole(LC-ESI/LTQ) and high performance liquid chromatography combined with ion trap-time of flight-mass spectrometry (LC-ESI/IT-TOF).Samples were separated by Hypersil BDS C_(18) and symmetry Shield columns, respectively, and 0.01% formic acid aqueous(A) and methanol(B) were used as mobile phase with gradient elution.Electros pray ionization mass spectrometric(ESI) source was used and operated in positive ion mode.When chickens were orally administered with mequindox at dosage of 20 mg/kg, blood samples were collected from the brachi al vein.Mequindox and its metabolites were extracted by the mixture of acetonitrile and acetoacetate (3:2, V/V).After solvent evaporated, the residue was dissolved in 30% methanol aqueous and the solution was detected by LC/IT-TOF MS and LC-ESI/LTQ.The molecule weight from LC-ESI/IT-TOF was analyzed by software Shimadzu's Composition and the mass chromatogram from LC-ESI/LTQ was analyzed by software Xcalibur 2.0.7.According to the molecular weight and MS~n data, referring the metabolic reaction rules, five chemical structures of mequindox related metabolites in chicken plasma were identified.Metabolites (M1-M4) were synthesized to verify the structure of metabolites.The metabolites are 3-methyl-2-(1-hydroxy) ethyl-qui-noxaline-N~1,N~4-dioxide(Ml), 3-methyl-2-(1-hydroxy) ethyl-quinoxaline-N~4-oxide(M2), 3-methyl-2-acetyl-quinoxaline-N~4-oxide, 3-methyl-2-acetyl-quinoxaline (M4), 3-hydroxymethyl-2-(1-hydroxy) ethyl-quinoxa-line-N~1,N~4-dioxide (M5).