Mechanism of Fasting-Induced Suppression of Acetaminophen Glucuronidation in the Rat
Acetaminophen overdosage, taken either as a suicidal gesture or as an accidental poisoning, is a significant clinical entity and one that appears to be growing in incidence. Results from a recent study have shown that the percentage of total drug-related deaths associated with acetaminophen in England and Wales rose dramatically from 3.8% in 1973 to 21% in 1980; further, the number of acetaminophen-associated deaths was the highest of all drug-related deaths for the years 1978 to 1980 (1). Thus there is a need to define more clearly the reasons for differences in patient responsiveness and to develop new treatment regimens to decrease the severity of liver failure.
KeywordsBlood Glucose Level Reactive Metabolite Glycogen Level Glycogen Deposition Increase Blood Glucose Level
Unable to display preview. Download preview PDF.
- 9.L.F. Prescott, Kinetics and metabolism of paracetamol and phenacetin, Brit. J. Pharmacol. 10: 291S (1980).Google Scholar
- 11.D.J. Jollow, S. Roberts, V. Price and C. Smith, Biochemical basis for dose response relationships in reactive metabolite toxicity, in “Biological Reactive Intermediates II: Chemical Mechanisms and Biological Effects”, R. Snyder, D. V. Parke, J.J. Kocsis, G. Gibson amd D.J. Jollow, ed., Plenum Press, New York (1982).Google Scholar
- 13.C. Smith, and D.J. Jollow, Potentiation of acetaminophen induced liver necrosis in hamsters by galactosamine, Pharmacologist 18: 156 (1976).Google Scholar
- 14.V.F. Price and D.J. Jollow, Acetaminophen hepatotoxicity: Reduced susceptibility of diabetic rats, Pharmacologist 22: 245 (1980).Google Scholar
- 17.R.G. Thurman and F.C. Kauffman, Factors regulating drug metabolism in intact hepatocytes, Pharmacol. Rev. 31: 229 (1980).Google Scholar
- 23.A.I. Winegrad and C.L. Burden, Hyperactivity of the glucuronic acid pathway in diabetes mellitus. Trans. Assoc. Am. Physicians 75: 158 (1965).Google Scholar
- 29.V.F. Price, M.G. Miller and D.J. Jollow, Mechanism of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat, Biochem. Pharmacol. Submitted.Google Scholar
- 30.V.F. Price and D.J. Jollow, Mechanism of fasting-induced suppression of acetaminophen glucuronidation in the rat, Biochem. Pharmacol. Submitted.Google Scholar
- 35.J.A. Hinson, H. Han-Hsue, J.B. Mays, S.J. Holt, P. McLean and B. Ketterer, Acetaminophen-induced alterations in blood glucose and blood insulin levels in mice, Res. Commun. Chem. Path. Pharmacol. 43: 381 (1984).Google Scholar
- 36.V.F. Price and D.J. Jollow, Acute glucose does not reverse fasting-induced suppression of acetaminophen glucuronidation in the rat. Biochem. Pharmacol. Submitted.Google Scholar