Abstract
We kinetically analyzed the disposition of l-carnitine of juvenile visceral steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism of the systemic l-carnitine deficiency of JVS mice. There were significant differences in the plasma concentration-time course of total radioactive carnitine (l-[3H]carnitine, [acetyl-3H]carnitine, and other [acyl-3H]carnitines) between normal and JVS mice after a single i.v. or p.o. administration ofl-[3H]carnitine (250 ng/kg). The oral bioavailability of l-[3H]carnitine in JVS mice (0.341) was about half of that in normal mice (0.675). The cumulative urinary excretion of total radioactive carnitine in JVS mice was about 10-fold more than that in normal mice, and the total clearance of unchanged l-[3H]carnitine for JVS mice (6.70 ml/min) was significantly higher than that for normal mice (2.45 ml/min). The distribution volume at the steady state of unchanged l-[3H]carnitine in JVS mice (1.10 liters/kg) was significantly smaller than that in normal mice (8.16 liters/kg). At 4 h after an i.v. administration, the apparent tissue-to-plasma concentration ratios of unchangedl-[3H]carnitine for various tissues of JVS mice, except for brain, were about one half to one 20th of those in normal mice. In conclusion, this in vivo disposition kinetic study ofl-carnitine supports the previous in vitro finding that thel-carnitine transporter is absent or functionally deficient in JVS mice because the renal reabsorption, the intestinal absorption, and the apparent tissue-to-plasma concentration ratios in JVS mice are significantly lower than those in normal mice. The JVS mouse should be a useful experimental model for studying carnitine deficiency diseases.
Footnotes
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Send reprint requests to: Dr. A. Tsuji, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-0394, Japan. E-mail:tsuji{at}kenroku.kanazawa-u.ac.jp
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↵1 This work was supported in part by a grant in-aid for Scientific Research from the Ministry of Education, Science Sports and Culture, Japan.
- Abbreviations:
- JVS
- juvenile visceral steatosis
- TLC
- thin-layer chromatography
- Vdss
- distribution volume at the steady state
- CLtot
- plasma total clearance
- Kp, app
- apparent tissue-to-plasma concentration ratios
- Received July 27, 1998.
- Accepted November 12, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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