Effects of acute ethanol exposure on polyamine and gamma-aminobutyric acid metabolism in the regenerating liver.
Recently, it has been suggested that ethanol-induced inhibition of liver regeneration results from decreases in hepatic putrescine levels and/or increases in hepatic gamma-aminobutyric acid (GABA)ergic activity. Because putrescine can be metabolized by diamine (DAO) and monoamine (MAO) oxidases to GABA, we documented the effects of acute ethanol exposure on hepatic MAO or DAO activity following partial hepatectomy (PHx) in rats. We also documented the effects of ethanol on GABA transaminase (GABA-T), the enzyme responsible for GABA metabolism in the liver, and tissue putrescine and GABA levels. Adult, male Sprague-Dawley rats (200-250 g) were treated with either ethanol (3 g/kg) or equal volumes of saline by gastric gavage 1 h prior to a 70% PHx or sham surgery. Rats were then sacrificed (n = 5-7/group) at various times (0-72 h) post-PHx. Enzymatic activity and putrescine/GABA levels were determined by standard isotopic techniques and high-performance liquid chromatography respectively. Hepatic DAO activities in ethanol-treated rats were transiently higher than in saline-treated controls (30% increases at 6 h, p < 0.05). Hepatic MAO and GABA-T activities in acute ethanol-treated rats were essentially identical to saline-treated controls. Although hepatic putrescine levels were similar in ethanol- and saline-treated rats, hepatic GABA levels were approximately three times higher in ethanol-treated rats at 12 and 24 h post-PHx (p < 0.0001). In conclusion, the results of this study indicate that acute ethanol exposure has a limited effect on the enzymatic conversion of putrescine to GABA following partial hepatectomy in the liver. The results also indicate that increased GABAergic inhibition rather than decreased putrescine stimulation is more likely to play a role in ethanol-induced inhibition of hepatic regeneration.
Lou
G
G
Department of Medicine and Pharmacology, University of Manitoba, Health Sciences Centre, Winnipeg, Canada.
Zhang
M
M
Minuk
G Y
GY
D000612:4-Aminobutyrate Transaminase / Q000187:drug effects / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000378:metabolism
D002492:Central Nervous System Depressants; D011073:Polyamines; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D000612:4-Aminobutyrate Transaminase