Studies on cytochrome oxidase in carbon tetrachloride treated rats

Cytochrome c oxidase was purified from control and CCl4 treated rats and its kinetic properties were studied. The activity of the enzyme was inhibited by 51% in CCl4 (4 g per kg body weight for 24 hr) treated rats. Studies on the kinetic properties showed that the K(m) of the enzyme increased by 60% while Vmax decreased by 44% in CCl4 treated rats compared to controls. The content of cytochrome aa3 was decreased by 34% while cytochrome b and c were not affected by CCl4 treatment. Phosphatidylcholine, phosphatidylethanolamine and cardiolipin were decreased significantly by 40%, 49% and 60% respectively in CCl4 treated rats. A decrease in the cytochrome aa3 content and a change in the lipid environment of the membrane are probably responsible for a decreased rate of electron transfer from cytochrome c to oxygen.     

L-tryptophan administration promotes the reversion of pre-established chronic liver injury in rats treated with carbon tetrachloride

We examined the effect of L-tryptophan (Trp) administration on the reversion of CCl(4)-induced chronic liver injury after hepatotoxicant withdrawal in rats. When rats treated with CCl(4) twice a week for 6 weeks were released from CCl(4) treatment for 2 weeks, there was an incomplete reversion of liver injury. The reversion was enhanced by 2 weeks of daily intraperitoneal administration of Trp (50 mg/kg body weight), starting just after CCl(4) withdrawal. There were increases in the levels of thiobarbituric acid reactive substances, an index of lipid peroxidation, Ca(2+), triglycerides, and Trp, and decreases in tryptophan 2,3-dioxygenase activity and serum triglyceride concentrations in the liver of rats treated with CCl(4) for 6 weeks. Serum albumin concentrations and in vitro hepatic protein synthesis activity did not change in the CCl(4)-treated rats. The changes in the CCl(4)-treated rats were partially attenuated 2 weeks after CCl(4) withdrawal. The attenuation was enhanced by 2 weeks of daily Trp administration. The increases in hepatic thiobarbituric acid reactive substances and triglycerides and the decreases in hepatic tryptophan 2,3-dioxygenase activity and serum triglyceride concentrations observed 2 weeks after CCl(4) withdrawal were almost completely attenuated by Trp administration. In vitro hepatic protein synthesis in CCl(4)-treated and untreated rats was increased by 2 weeks of daily Trp administration. These results indicate that Trp administration promotes the reversion of pre-established chronic liver injury in rats treated with CCl(4,) and suggest that Trp exerts this effect by enhancing the improvement of several parameters of liver dysfunction associated with chronic liver injury and by stimulating hepatic protein synthesis.     

Lipoperoxidation after carbon tetrachloride poisoning in rats previously treated with antioxidants

Propyl gallate (PG), reduced glutathione (GSH) and N,N′-diphenyl-p-phenylenediamine (DPPD), administered to rats prior to carbon tetrachloride, protect against hepatic fat infiltration until the fourth hour after poisoning. This effect does not seem to be mediated by a block in lipid mobilization from depot fat.A preliminary treatment with DPPD succeeds in inhibiting the double bond shifting in liver microsomal lipids within 30 min after dosing with CCl₄. The early peroxidative alteration occurs at the normal rate after the administration of either GSH or PG. The amount of lipid-bound radiocarbon and of ¹⁴CO₂ exhaled within 2 h after intragastric ¹⁴C-labelled carbon tetrachloride is not affected by the preliminary protection with the antioxidants.CCl₄ metabolites and/or lipoperoxides impair the in vitro combination of serum apoprotein with lipid. No changes are observed when lipoperoxidation is inhibited by antioxidants.These findings are interpreted as a support for the hypothesis that the possible contribution given by the enhancement of lipid peroxidation to the pathogenesis of CCl₄-induced fatty liver could depend on further structural and functional alterations occurring in the cytoplasmic environment of hepatocytes rather than the early radical attack onto the unsaturated lipids of liver microsomes. The functional integrity and the supply of the protein carrier for the triglyceride secretion mechanisms could be considered a target of the hepatotoxic action of CCl₄, at the molecular level.     

Fructose bisphosphatase activity in the serum of rats treated with carbon tetrachloride

In this work, fructose bisphosphatase activity in the serum of rats treated by different carbon tetrachloride doses was measured. Fructose bisphosphatase activity increased very significantly with respect to the control animals in all groups assayed. The severe reduction of the activity measured in the presence of adenosine-5'-monophosphate and its stability when measured in the presence of 1-p-bromotetramisole oxalate support its specific origin. These data suggest that serum FBPase activity measurement could be used as a biochemical marker in the diagnosis of hepatocellular injury.     

Changes in liver and muscle glycogen in rats treated with serotonin

The authors have put in evidence that the 5-HT (20 mg/Kg b.w.) injected intraperitoneally in four days fasting rats and drinking water, causes an almost complete glycogenolysis in liver and muscles. When the 5-HT is injected in four days fasting rats but drinking a water solution (20%) of glucose, the amount of glycogen, in both organs, is marked increased.     

Hepatotrophic growth factor in blood of mice treated with carbon tetrachloride

The presence of a human hepatocyte growth factor (hHGF)-like DNA-synthesis promoter in platelet-poor serum of mice with liver injury was examined. Activity of the serum for stimulating DNA synthesis in cultured rat hepatocytes was low in untreated or vehicle-treated mice, but markedly increased 24 h after carbon tetrachloride administration and then dropped to normal levels prior to the peak of liver DNA synthesis. The effect of the serum was additive with the maximal effects of mouse and human epidermal growth factors, but not with that of hHGF. The growth-stimulating factor in the mouse serum, like hHGF, had affinity for heparin and was heat-labile. These results indicate that the level of a serum hHGF-like hepatocyte growth factor increased in mice treated with carbon tetrachloride prior to liver regeneration.     

Rapid induction of liver cirrhosis in rats by treatment with ethanol, carbon tetrachloride and progesterone

The administration of progesterone increases the degree of liver cirrhosis in rats treated with CCl4 and ethanol. Pseudolobulation with large amount of interstitial fibrosis are obtained after only 6 weeks of treatment. The ability of progesterone to suppress collagenase activity is supposed to be responsible of the strong increase of cirrhosis.     

Regional brain GABA metabolism and release during hepatic coma produced in rats chronically treated with carbon tetrachloride

Hepatic coma was induced in rats chronically treated with CCl₄, by means of a single injection of ammonium acetate. The activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), as well as the synaptosomal uptake and release of [³H]GABA, were measured in the following brain areas of the comatose rats: cortex, striatum, hypothalamus, hippocampus, midbrain and cerebellum. Hepatic coma was associated with a general decrease of GAD activity, whereas GABA-T activity was diminished only in the hypothalamus, striatum and midbrain. During hepatic coma, the K⁺-stimulated [³H]GABA release was notably diminished in the striatum and cerebellum, whereas a significant increase was observed in the hippocampus. [³H]GABA uptake increased in most regions after CCl₄ treatment, independently of the presence of coma. The results indicate that GABAergic transmission seems to be decreased in most cerebral regions during hepatic coma.