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

The research paper focuses on the effects of aging on the hepatic microsomal scaling factor and hepatocellularity number in horses. The study examines this by comparing total protein and cytochrome (CYP) P450 content in microsomes and hepatocytes with the content in the liver, thus determining the scaling factor values for possible extrapolation of hepatic metabolic clearance for xenobiotics in horses.

Methodology

• The study evaluated scaling factors by comparing total protein content and CYP P450 content in microsomes and cryopreserved hepatocytes to the corresponding substance content in the liver of horses.
• From this comparison, values for microsomal protein per gram of liver (MPPGL) and hepatocellularity number per gram of liver (HPGL) were determined by utilizing the CYP P450 content method and the total protein method.

Results

• Results reflect a non-linear, inverse relationship between the horse’s age and MPPGL and HPGL. As a horse ages from one to twenty years, the size of its liver cells decrease. Then, the cell size increases with age until the hepatocytes match the size found in young horses.
• There’s a significant correlation found where the density of hepatocytes is inversely related to the size of the hepatocytes, which means that as the size of hepatocytes increases, their density decreases, and vice versa.

Conclusion

• This research provides the scientific community with the first carefully collected and analyzed set of data that illustrates the relationship between the size of hepatocytes and HPGL in horses.
• This novel data not only contributes to our understanding of horse liver cell aging but also aids in the future in vitro-in vivo extrapolation of hepatic metabolic clearance calculation for xenobiotics in horses.