The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats

Abstract

Serum and hepatic polyamine concentrations in-inhibitory properties (5-7 1. Although the mechanism eluding putrescine, spermidine and spermine were whereby GABA inhibits cell growth has yet to be documented at Various time intervals after Partial determined, GABA has been reported to alter ornithine hePatectomY in rats treated with GABA (500 PdW decarboxylase (ODC) activity, the enzyme primarily body wt) Or isotonic saline. Aside from a transient responsible for polyamine synthesis (8, 9). Of interest, effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the animals and with fulminant increase in hepatic putrescine concentrations that hepatic failure, a condition in which hepatic regeneroccurs after partial hepatectomy such that levels were ative activity may be suppressed (10-13). The PuTose of 646, 74% and 1ooo/t lower than in saline-treated con-this study was to determine whether systemic serum trols on days 1, 2 and 3 after partial hepatectomy GABA concentrations similar to those reported in (p < 0.005, p < 0.01 and p < 0.05, respectively). Sper-animals and humans with liver failure interfere with midine and spermine concentrations in the liver were hepatic polymine synthesis. not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concen-METHODS AND MATERIALS trations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented Animals and Surgery. Adult male Sprague-Dawley rats after GABA treatment, Although ornithine decarhx-(200 to 250 g m ) were obtained from Charles River Canada ylase messenger RNA levels were ornithine (St. Constant, Quebec). The animals were housed in a decarbowlase enzyme was si@ficantly intemperature-and light-controlled room (7 AM to 7 PM). Seventy hibited 12 after hepatectomy in GABApercent partial hepatectomies were performed with the antreated rats with saline-treated controls. imals under light ether anesthesia between 9 and 12 AM as me results of this study indicate that GABA inhibits described by Higgins and Anderson (14). Sham hepatectomies hepatic putrescine synthesis at a posttranscriptional consisted of laparotomy and exteriorization of an identical level in rats after hepatectomy. amount of liver tissue for a similar time as that required for a could help to explain the impairment in hepatic regen-70% partial hepatectomy. erative activity that occurs in patients with elevated Study Croups. In GABA-treated animals, preliminary exserum GABA concentrations and fdminant hepatic periments in which serum GABA concentrations were deterfailure. (HEPATOLOGY 199 1; 14:685-689.) mined 4 h r after intraperitoneal GABA administration (peak level) and immediately before the next dose of GABA (trough level) were used to derive the dosage of GABA required to promotors Of provide serum concentrations that approximate those reported ProkWotic and eukWotic cells (1). Previous data in animals and humans with fulminant hepatic failure (5 to 30 indicate that polyamines and putr...

The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure

“…16 We have previously documented that at serum concentrations similar to those described in animal models and humans with FHF, GABA significantly inhibits hepatic regenerative activity. 7,9 We have also documented that GABA' s inhibitory effects are likely mediated via activation of hepatocyte membrane GABA A receptors. 10 Recently, we reported that ciprofloxacin reverses these inhibitory effects in ethanoland carbon tetrachloride-induced models of hepatic injury.…”

“…5,6 ␥-Aminobutyric acid (GABA) is a potent inhibitory amino acid neurotransmitter that inhibits the growth of normal and malignant cells. 7,8 We have previously reported that elevated serum concentrations of GABA similar to those documented in animals and humans with FHF inhibit hepatic regenerative activity in the rat. 9 Recently, we reported that ciprofloxacin, a fluroquinolone antibiotic with GABA A receptor antagonist properties, reverses the inhibitory effects of acute ethanol exposure on hepatic regeneration and the extent of fibrosis in a carbon tetrachloride model of cirrhosis in rats.…”

Liver regeneration after hepatic ischemia and reduced liver autotransplantation in the rat

“…The immediate effects of portal occlusion on plasma levels of glucagon do not appear to have been studied, but certainly, plasma glucagon levels are elevated significantly within 30 min of portacaval shunting (181, which would account for the delay in animals in group 3 of this study. Other substances that interfere with the activity of ODC, such as y-aminoisobutyric acid (19) do not appear to have been measured after portal occlusion.…”

The Beneficial Effect of N-Acetylcysteine and Ciprofloxacin Therapy on the Outcome of Ischemic Fulminant Hepatic Failure

“…Although the precise mechanism by which ciprofloxacin enhances hepatic regeneration has yet to be determined, this agent's potent GABA A receptor antagonist properties may be relevant [16]. GABA is known to inhibit liver regeneration and is highly elevated in patients and animals with FHF [5,17]. We have shown previously that ciprofloxacin enhances liver regeneration in an animal model of fulminant hepatitis, and increases survival rate as well [18].…”