Caffeine demethylation measured by breath analysis in experimental liver injury in the rat

• Published in: Journal of hepatology Vol. 22; no. 1; pp. 82 - 87
• Main Authors: Schaad, Heinz J., Renner, Eberhard L., Wietholtz, Hubertus, Arnaud, Maurice J., Preisig, Rudolf
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 1995; Elsevier
• Subjects: Animals; Bile duct ligation; Biological and medical sciences; Breath analysis; Breath Tests; Caffeine - metabolism; Caffeine - pharmacokinetics; Caffeine demethylation; Carbon Dioxide; Carbon Radioisotopes; Gastroenterology. Liver. Pancreas. Abdomen; Hepatectomy; Liver disease models; Liver Diseases - metabolism; Liver function; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Methylation; Other diseases. Semiology; Portocaval anastomosis; Rat; Rats; Rats, Sprague-Dawley; Respiration; Liver function; Caffeine demethylation; Rat; Bile duct ligation; Breath analysis; Portocaval anastomosis; Liver disease models; Hepatectomy; Demethylation; Vertebrata; Breath test; Mammalia; Animal; Liver; Rodentia; Digestive diseases; Hepatic disease; Lesion; Experimental study
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/0168-8278(95)80264-9

To assess the effects of experimental liver injury on caffeine metabolism, 1 μCi/kg b.w. of [3-methyl 14C]-caffeine (together with 5 mg/kg b.w. of the cold compound) was injected i.p. to four different experimental groups and respective controls of unanesthetized male Sprague-Dawley rats. Exhaled 14CO 2 was completely collected during 4 h and peak exhalation rate and fraction of dose recovered were calculated. 1 3 hepatectomy affected 14CO 2 exhalation to a limited extent, decreasing solely peak exhalation rate ( p<0.05 compared to sham-operated controls). 2 3 hepatectomy, on the other hand, resulted in significant reduction ( p<0.01) in both peak exhalation rate (by 59%) and fraction of dose recovered (by 47%), that were proportionate to the loss of liver mass (59%). End-to-side portocaval shunt led to the well-documented hepatic “atrophy”, liver weight being diminished on average to 50% within 2 weeks of surgery; however, reductions in peak exhalation rate (by 75%) and fraction of dose recovered (by 64%) were even more pronounced. Finally, 48 h bile duct ligation was equivalent to “functional 2 3 hepatectomy”, peak exhalation rate (by 65%) and fraction of dose recovered (by 56%) being markedly diminished despite increased liver weight. These results indicate that 14CO 2 exhalation curves following administration of specifically labelled caffeine are quantitative indicators of acute or chronic loss of functioning liver mass. In addition, the 3-demethylation pathway appears to be particularly sensitive to the inhibitory effects of cholestasis on microsomal function.