Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis

Hepatocellular Alterations after Intraportal Transplantation of Ovarian Tissue in Ovariectomized Rats

“…The following enzymes were investigated: glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malic enzyme (ME), mitochondrial glycerol-3-phosphate dehydrogenase (mG3PDH), cytochrome c oxidase (COX), acid phosphatase (AP), and ␥-glutamyltransferase (GGT). [21][22][23][24] Furthermore, serial cryostat sections were stained for basophilia with toluidine blue, for the presence of neutral lipids with Fettrot B, and for the presence of glycogen with the PAS reaction.…”

Hepatocellular Glycogenosis and Hepatic Neoplasms

“…It has been known for decades that human patients suffering from inborn hepatic GSD, mostly that of type I (von Gierke's disease), which is due to a genetic defect in glucose-6-phosphatase, have an increased risk to develop hepatocellular adenomas and carcinomas when they pass through adolescence (Bannasch et al 1984;Bianchi 1993;Limmer et al 1988;Lerut et al 2003;Mason and Anderson 1955;Wolfsdorf and Weinstein 2003; see the preceding for further literature). GSDs related to glycogen phosphorylase, namely, GSD VI (phosphorylase deficiency, Hers disease) and GSD IX (phosphorylase kinase deficiency), are much less frequent than GSD I, but even in these rare diseases hepatic adenomas have occasionally been observed in adolescence (Wolfsdorf and Weinstein 2003;Weinstein 2010).…”

“…Compelling evidence for the preneoplastic nature of the focal hepatic glycogenosis (appearing as clear cell lesions in conventional, H&E-stained tissue sections) has been provided by many laboratories (Bannasch 1968;Bannasch, Mayer, and Hacker 1980;Bannasch et al 1995;Cattan et al 2000;Dombrowski, Bannasch, and Pfeifer 1997;Dombrowski, Mathieu, and Evert 2008;Hacker et al 1982;Kim et al 1991;Moore and Kitagawa 1986;Nehrbass, Klimek, and Bannasch 1998;Radaeva et al 2000;Toshkov, Chisari, and Bannasch 1994;Williams et al 1976; see the preceding for further literature). It has been demonstrated by biochemical approaches in situ in animal models of chemical, viral, and hormonal hepatocarcinogenesis, and in acquired human liver diseases, that the focal hepatic glycogenosis is regularly associated with a reduction in the activity of the two key enzymes involved in glycogen breakdown, namely, the glycogen phosphorylase and the glucose-6-phosphatase (Bannasch et al 1984Hacker et al 1982;Kitagawa 1986, Toshkov, Chisari, andBannasch 1994;Radaeva et al 2000;Dombrowski, Bannasch, and Pfeifer 1997;Dombrowski, Mathieu, and Evert 2008). It would be of great interest to know whether the activity of glucose-6-phosphatase is reduced in addition to that of glycogen phosphorylase in the model presented by Floettmann and colleagues.…”

“…The authors discussed that the ''glucose-derived energy appeared to be shifted from glycogenosis to de novo lipogenesis'' and felt that ''drug holidays'' might help to avoid fat accumulation and its adverse effects on the liver. It is important to realize, however, that it has been shown in the stop model of rat hepatocarcinogenesis that the transient storage of fat associated with the focal glycogenosis occurs only weeks and months after withdrawal of the carcinogen, indicating a persisting metabolic disturbance that is closely related to advanced preneoplasia or early neoplasia (Bannasch 1968;Bannasch, Mayer, and Hacker 1980;Bannasch et al 1984). The metabolic aberrations in the acquired preneoplastic glycogenotic lesions are never limited to changes in the amount or activity of one enzyme such as glycogen phosphorylase but show a complex pattern resembling an effect of insulin (Bannasch, Klimek, and Mayer 1997;Dombrowski, Bannasch, and Pfeifer 1997;Dombrowski, Mathieu, and Evert 2008;Nehrbass, Klimek, and Bannasch 1998;Radaeva et al 2000).…”

“…It would be of great interest to know whether the activity of glucose-6-phosphatase is reduced in addition to that of glycogen phosphorylase in the model presented by Floettmann and colleagues. In all experimental models of hepatocarcinogenesis, the transformation of the glycogenotic preneoplastic into the neoplastic cell populations requires a long lag period and is characterized by a fundamental metabolic shift resultingamong many other subcellular changes-in a gradual reduction of the glycogen initially stored in excess (Bannasch 1968;Bannasch, Mayer, and Hacker 1980;Bannasch et al 1984Bannasch et al , 1995Moore and Kitagawa 1986;Radaeva et al 2000;Toshkov, Chisari, Toxicologic Pathology, 38: 1000-1002, 2010 Copyright # 2010 by The Author(s) ISSN: 0192-6233 print / 1533-1601 online DOI: 10.1177/0192623310378026 and Bannasch 1994;Dombrowski, Bannasch, and Pfeifer 1997;Dombrowski, Mathieu, and Evert 2008). This metabolic shift is often accompanied by a transient accumulation of neutral fat.…”