PMID: 7086685Jun 1, 1982Paper

Cholestatic effect of harmol glucuronide in the rat. Prevention of harmol-induced cholestasis by increased formation of harmol sulfate

The Journal of Pharmacology and Experimental Therapeutics
K R KrijgsheldG J Mulder

Abstract

Harmol, a phenolic compound of low molecular weight, is conjugated either with glucuronic acid or sulfate. A clear relationship is observed between the metabolism of harmol and the occurrence of cholestasis: high concentrations of harmol glucuronide in bile induced a complete stop of bile flow, both in the rat in vivo and in the perfused rat liver. Intravenous infusion of harmol (250 mumol/hr/kg b.wt.) in vivo in the rat considerably decreased the availability of sulfate and, consequently, the amount of harmol sulfate excreted in bile and urine; this decrease was compensated for by an increase in glucuronidation, which caused complete cholestasis when the concentration of harmol glucuronide in bile became of the order of 20 mM. A sufficient supply of sulfate by infusion of sodium sulfate prevented the decrease in sulfation and the increase in glucuronidation and no cholestasis occurred. Low sulfate availability in rats fed a low-protein diet decreased the time of harmol infusion required for cholestasis to occur. Alleviation of the cholestasis in low-protein diet-fed rats was observed when after 2 hr of infusion of harmol additional sulfate was supplied. In the single-pass perfused rat liver, cholestasis occurred when large amo...Continue Reading

Related Concepts

Harmol hydrochloride
Plant alkaloid
Cholestasis
Diet
Glucuronic Acids
Harmine
Liver
August Rats
Sulfates, Inorganic

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