Short communicationAging, acute oxidative injury and hepatocellular glucose transport in the rat
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Rethinking toxicity testing: Influence of aging on the outcome of long-term toxicity testing and possible remediation
2020, Food and Chemical ToxicologyCitation Excerpt :Other changes that may affect the pharmacokinetics and/or pharmacodynamics of a chemical include aging-related reduction in the homeostatic reserve, efflux transporters, repair mechanisms, and apoptosis (Bales and Ritchie, 2002; Baum et al., 2007; Butler and Begg, 2008; Dodman, 2015; Elmadfa and Meyer, 2008; Hilmer, 2008; Houtkooper et al., 2011; Lichtman and Boparai, 2008; McLean and Le Couteur, 2004; Speakman et al., 2003; Toornvliet et al., 2006; Wolden-Hanson, 2010; Zhang et al., 2010). The volume of hepatocytes increases through maturity and subsequently becomes smaller, reducing the size of the liver in addition to an increasing the volume of dense body compartment and losing smooth endoplasmic reticulum (Le Couteur et al., 1995; Schmucker, 1990; Schmucker et al., 1978). The aging-related reduction in blood flow to the liver results in declined liver function and altered pharmacokinetic profiles of chemicals undergoing hepatic metabolism (Anantharaju et al., 2002; Frith et al., 2009; Hilmer, 2008; Hilmer et al., 2005; Ito et al., 2007; Kim et al., 2015; Le Couteur and McLean, 1998; Le Couteur et al., 2008; Marchesini et al., 1988; Mitchell et al., 2011b; Schmucker, 1998, 2001, 2005; Wynne et al., 1989a, 1989b; Zoli et al., 1999).
The effect of oxidative injury on hepatocellular influx of leucine in the rat
1996, International Hepatology CommunicationsAge-related pseudocapillarization of the liver sinusoidal endothelium impairs the hepatic clearance of acetaminophen in rats
2011, Journals of Gerontology - Series A Biological Sciences and Medical Sciences