The effect of therapeutic doses of paracetamol on liver function in the rat perfused liver.
The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0.02 g kg-1 paracetamol daily for ninety days. The livers of animals in the control group and in one of the experimental groups were perfused with a medium containing pyruvate. The animals in the second experimental and control group were perfused with a medium containing bromosulphthalein (10 mg/100 mL). The livers of the third experimental and control group were subjected to histological examination. The rate of glucose formation and glucose concentrations were decreased, while, lactate levels and lactate: pyruvate ratios were increased in paracetamol-treated rats. The mean concentration of bromosulphthalein in the perfusate and biliary excretion of the dye were decreased. Macro and micro vesicular fatty change was present in the livers of paracetamol-treated rats. This study demonstrates that chronic administration of therapeutic doses of paracetamol to rats adversely affects liver function, as evidenced by impaired gluconeogenesis and bromosulphthalein clearance from the perfusate, and excretion of the dye into the bile, and provides histological evidence of hepatic damage in rats.
Khedun
S M
SM
Department of Experimental and Clinical Pharmacology, University of Natal Medical School, Durban, South Africa.
Maharaj
B
B
Leary
W P
WP
Naicker
T
T
D000082:Acetaminophen / Q000494:pharmacology*; D000818:Animals; D001706:Biopsy; D005943:Gluconeogenesis / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008853:Microscopy; D008954:Models, Biological; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000493:pharmacokinetics
D013448:Sulfobromophthalein; D000082:Acetaminophen