The effects of aging on hepatic microsomal scaling factor and hepatocellularity number in the horse

Scaling factor values for the in vitro-in vivo extrapolation of hepatic metabolic clearance for xenobiotics have not yet been determined in horses. Scaling factors were determined by comparing the total protein and or CYP P450 content in microsomes and cryopreserved hepatocytes against the content in the liver. Microsomal protein per gram of liver (MPPGL) and hepatocellularity number per gram of liver (HPGL) using CYP P450 content method ranged 41 - 73 mg/gram of liver (mean= 57 mg/gram of liver, n=39) and 146 - 320 × 106 cells/g of liver (mean = 227× 106 cells/g of liver, n=18), respectively; and 156 - 352 × 106 cells/g of liver (mean = 232× 106 cells/g of liver) using total protein method. A non-monotonic and inverse relationship between age and MPPGL and HPGL, respectively, was observed. Between 1 and 20 years of age the liver cell size decreases as age increases. Subsequently, the cell size increases until the hepatocytes of the oldest horses approached the size found in the youngest horses. Hepatocyte density was inversely related to the size of the hepatocytes. This study provides the first extensive and comprehensive data demonstrating the relationship between the size of hepatocytes and HPGL in any species