The effects of ethanol on putrescine and GABA metabolism in the liver
| dc.contributor.author | Lou, Ganlu | en_US |
| dc.date.accessioned | 2007-05-15T15:23:56Z | |
| dc.date.available | 2007-05-15T15:23:56Z | |
| dc.date.issued | 1997-05-01T00:00:00Z | en_US |
| dc.degree.discipline | Pharmacology and Therapeutics | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | The mechanisms responsible for ethanol-associated inhibition of liver regeneration following partial hepatectomy remain unclear. Previous data indicate that ethanol-induced decreases in hepatic putrescine levels and enhancement of hepatic gamma-aminobutiric acid (GABA)ergic activity play important pathophysiologic roles. Of interest is the fact that GABA is a product of putrescine metabolism via either diamine oxidase (DAO) or monoamine oxidase (MAO) enzyme activity. Whether ethanol alters the process of polyamine to GABA metabolism remains to be determined. Thus the purpose of this study was to determine the effects of ethanol on hepatic polyamine metabolism following partial hepatectomy. Hepatic DAO, MAO and GABA transaminase (GABA-T), the enzyme responsible for GABA metabolism, and levels of putrescine, GABA and other polyamines (spermidine and spermine) were determined in the livers of adult male Sprague-Dawley rats (200-250 g) which had been pretreated with a dose of either ethanol (5g/kg) to inhibit hepatic regeneration or equal volumes of saline by gastric gavage 1 h prior to a 70% partial hepatectomy or sham surgery. Rats were then sacrificed in groups (N = 4-9/group) at various times (0-48 hrs) post partial hepatectomy. Enzymatic activities were determined by radiochemical techniques and the levels of polyamines and GABA by high pressure liquid chromatograghy (HPLC). Hepatic DAO activities in acute ethanol exposed rats were consistently increased post partial hepatectomy when compared to saline exposed controls. Statistical significance was achieved at 48 h (ethanol vs. saline at 48 h; 260 $\pm$ 128 vs 135 $\pm$ 35 pmoles/mg protein/h (p $<$ 0.05)). Hepatic MAO activities were essentially identical in the two groups. Hepatic putrescine levels exhibited a biphasic pattern in the ethanol exposed group, i.e., slightly decreased hepatic putrescine levels during the earlier period, (6-12 h), while increased during the later period (24-48 h) post-partial hepatectomy, (ethanol vs. saline at 48 h; 15.2 $\pm$ 2.3 vs 8.8 $\pm$ 1.5 nmoles/g liver (p $<$ 0.05)). Hepatic GABA levels were also significantly increased in the ethanol exposed group at 48 h post partial hepatectomy (ethanol vs. saline at 48 h; 859 $\pm$ 168 vs 383 $\pm$ 97 nmoles/g liver (p $<$ 0.01)). GABA-T activities were increased and decreased significantly at 6 h and 48 h respectively, (ethanol vs. saline at 6 h; 40 $\pm$ 1.7 vs 30 $\pm$ 1.4 and 48 h; 21 $\pm$ 2.9 vs 32 $\pm$ 5.5 pmoles/mg protein/h (P $<$ 0.05 and 0.01 respectively)). Ethanol exposure had no consistent effects on hepatic spermidine or spermine levels. The results of this study provide further support for the hypothesis that the antiregenerative effects of ethanol on the liver may be mediated by increased hepatic conversion of putrescine to GABA and inhibition of GABA metabolism in a post-partial hepatectomy model of hepatic regeneration in rats. | en_US |
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| dc.format.extent | 184 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.format.mimetype | text/plain | |
| dc.identifier.uri | http://hdl.handle.net/1993/948 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.title | The effects of ethanol on putrescine and GABA metabolism in the liver | en_US |
| dc.type | master thesis | en_US |