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

Shibany, Khaled A.; T�temeyer, Sabine; Pratt, Stefanie L.; Paine, Stuart W.

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


Authors

Khaled A. Shibany

Stefanie L. Pratt

STUART PAINE Stuart.Paine@nottingham.ac.uk
Professor of Pharmacometrics



Abstract

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.

Journal Article Type Article
Acceptance Date Dec 1, 2018
Online Publication Date Dec 19, 2018
Publication Date Dec 19, 2018
Deposit Date Dec 11, 2018
Publicly Available Date Dec 20, 2019
Journal Xenobiotica
Print ISSN 0049-8254
Electronic ISSN 1366-5928
Publisher Taylor & Francis Open
Peer Reviewed Peer Reviewed
Volume 48
Issue 12
Pages 1237-1244
DOI https://doi.org/10.1080/00498254.2017.1413263
Public URL https://nottingham-repository.worktribe.com/output/1403817
Publisher URL https://www.tandfonline.com/doi/abs/10.1080/00498254.2017.1413263?journalCode=ixen20
Additional Information Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ixen20

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