The effect of therapeutic doses of paracetamol on liver function in the rat perfused liver

Abstract

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.

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

“…There was no evidence of liver cell necrosis. Such types of changes have also been observed by Khedun et al (27) in experimental rats treated with 2.5 mg/kg of INH for 90 days orally. A similar type of hepatic cell injury has been observed with valproic acid, tetracycline (28), and carbon tetrachloride (12).…”

The Isolated Perfused Rat Liver and its use in the Study of Chemical Kinetics: Quality and Performance Parameters

“…Adverse effects have been demonstrated in the IPRL using BSP kinetics as a biomarker by peroxisome proliferators (James and Ahokas, 1992 a,b), paracetamol (Khedun et al, 1993), and ischemia-reperfusion injury (Kukan et al, 1995).…”