Date of Award
Doctor of Philosophy
Dileep S. Sachan
Jane R. Savage, Donita L. Frazier, Walter R. Farkas, Roy E. Beauchene
Male Sprague-Dawley rats, 300-500g, were fed Purina rodent chow with or without a supplement of 0.5 % L-carnitine (CS or NS groups) for 5-7 days, after which they were given a single oral dose of methanol (2.25 g/kg), isopropanol (2.0 g/kg), ethylene glycol (5.56 g/kg), or ethylene glycol (5.56 g/kg) followed by ethanol (3.0 g/kg) 1 hour later in aqueous solutions. Serial blood and urine samples were collected over time and analyzed for the respective alcohols by gas chromatography. The data were subjected to pharmacokinetic analysis and statistical analysis.
There was significant reduction in blood methanol concentration in the CS group at 2 and 4 hours which was supported by the kinetic analysis: a lower area under the blood methanol curve, a lower absorption slope to the peak blood concentration and longer time to reach the peak concentration. The urinary excretion of methanol was significantly increased in the CS group at 2 and 4 hours post dosing.
There were no significant differences between the NS and CS groups for blood isopropanol concentrations at all time points. Following isopropanol administration the urine output was significantly higher in the CS than the NS animals which was reflected in higher total isopropanol excretion in the urine of the CS group. Urinary clearance of isopropanol was significantly higher in the CS than the NS group. Acetone appearance in blood was not significantly affected by carnitine, however, the excretion of acetone in the urine was enhanced due to higher urine volume of the CS group.
Blood ethylene glycol concentration curves were not significantly different between the NS and CS groups. Carnitine supplementation did not increase the urinary excretion of ethylene glycol or the urinary volume following ethylene glycol gavage.
Ethanol administration following a dose of ethylene glycol resulted in a higher blood ethylene glycol concentration and more rapid elimination of ethylene glycol from the blood of the CS animals compared to that from the NS animals. There were no differences in the urinary volumes or concentrations of ethylene glycol between the NS and CS animals. However, there was a marked rise in the urinary clearance of ethylene glycol in the CS group compared to the NS group. There were no differences in the blood ethanol concentration curves or urinary ethanol excretion of the NS and CS animals when ethanol was given after ethylene glycol.
It is concluded that supplementary L-carnitine offered protection against accumulation of methanol, isopropanol and ethylene glycol with ethanol in the early phase of their appearance in blood via increased urinary clearance of these alcohols.
Ruark Brothers, Robin Ann, "Effect of Carnitine on the Disposition of Alcohols. " PhD diss., University of Tennessee, 1989.