Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements.
Biologically based scaling factors have to be used to predict in vivo metabolic clearance of xenobiotics from data obtained in vitro. Although standard values for the hepatocellularity numbers for different species are used in the literature, detailed information on the determination of these values has only been presented for humans and rats, and somewhat different results have been obtained in different studies. The present work was undertaken in order to determine the number of hepatocytes per gram of liver for human, dog, rabbit, rat and mouse livers. Hepatocellularity numbers were calculated from the ratio between the liver protein concentration and the protein concentration in the corresponding hepatocyte suspension. For human, rabbit, rat and mouse livers, the hepatocellular values were in the same range, more precisely 139+/-25, 114+/-20, 117+/-30 and 135+/-10 million cells per gram of liver, respectively. However, for the dog liver, the corresponding value was as high as 215+/-45 million cells per gram. These values should be of importance during the scaling process of intrinsic clearance for xenobiotics in hepatocytes to in vivo hepatic clearance.
Sohlenius-Sternbeck
Anna-Karin
AK
Research DMPK, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, Sweden. anna-karin.sternbeck@astrazeneca.com
D000328:Adult; D000368:Aged; D000818:Animals; D002452:Cell Count; D015925:Cryopreservation; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004285:Dogs; D005260:Female; D022781:Hepatocytes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D011506:Proteins; D004247:DNA