Antihepatotoxic properties of uridine-diphosphoglucose in liver fluke infection. Experimental fascioliasis in the rat.

The antihepatotoxic properties of uridine-diphosphoglucose (UDPG, Toxepasi) have been evaluated in a well-established model of liver damage, the liver fluke infection (experimental fascioliasis in the rat), which causes a dramatic loss of the microsomal drug-metabolizing monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems as a consequence of peroxidative damage to microsomal membrane lipids. Administration of 100 mg/kg UDPG i.p. to the infested rat for the entire course of the infection (40 days) positively affects the parameters reflecting the integrity of the liver cell (serum glutamate-pyruvate, GPT and glutamate-oxaloacetate, GOT, transaminases) and the detoxifying capacity of the liver (cytochrome P-450, cytochrome b5, cytochrome P-450-dependent p-nitroanisole O-demethylase and aniline hydroxylase activities, and the p-nitrophenol glucuronidation) and greatly reduces the lipid peroxidative phenomen in membranes from whole liver (tissue malonic dialdehyde content) and in membranes of the microsomal fraction (conjugated diene absorption). As a consequence of this, the total lipid and phospholipid contents of the liver are restored, there is minimal loss of latency of GT enzyme(s), cytochrome P-450 conversion to cytochrome P-420 is fairly negligible and total liver glutathione content is also restored. Therefore, UDPG restores liver function by protecting the endoplasmic reticulum membranes from the oxidative stress resulting from activation of the CN-insensitive respiratory burst of the phagocytic cells consequent to Fasciola hepatica invasion, migration and growth. It is very likely that UDPG acts as an effective antilipoperoxidative agent through both direct (as demonstrated by our in vitro experiments) and indirect mechanisms (stimulation of the glycolytic pathway, and hence of the reducing equivalents----glutathione----vitamin E supply).(ABSTRACT TRUNCATED AT 250 WORDS)

Protection by uridine diphosphoglucuronic acid and DT-diaphorase against the cytotoxicity of polycyclic aromatic hydrocarbons isolated from a complex coal gasification condensate.

The cytotoxicities of polycyclic aromatic hydrocarbon (PAH) subclasses isolated from a complex organic mixture (coal gasification condensate) were studied in vitro in Chinese hamster ovary cells, in the presence of rat liver microsomes from animals pretreated with Aroclor. Toxicity was enhanced by microsomal metabolism and was inversely related to aromatic ring number. Rat liver cytosol, semipurified DT-diaphorase, and uridine diphosphoglucuronic acid decreased the cytotoxicity of a variety of PAH mixtures and representative PAH, as well as individual PAH metabolites. The results indicate that the in vitro toxicity of complex PAH mixtures is caused primarily by hydroxy-PAH and quinone metabolites of the predominant, nonmutagenic two- and three-ring PAHs.

[Uridine diphosphate glucose in acute viral hepatitis]. / L'uridin-5'-difosfoglucosio in corso di epatite virale acuta.

200 mg UDPG or placebo respectively were administered after an observation period of 1 week to two randomly constructed groups of patients aged 15-35 yr with acute viral hepatitis but no prior history of disease. In the treated patients, mean decreases were most marked and most rapid in the case of SGOT, SGPT, alkaline phosphatase and total bilirubinaemia. These results offer good reason for supposing that UDPG can be usefully employed in the management of acute viral hepatitis.

[The use of different liver-protective substances in the course of antitubercular chemotherapy and their effectiveness in preventing and countering the appearance of metabolic and functional liver changes Clinico-statistical studies]. / Impiego di differenti sostanze di pertinenza epatica in corso di chemioterapia antitubercolare e loro efficacia nel prevenire e contrastare l'insorgenza di alterazioni metabolico-funzionali. Ricerca clinico-statistica.

An open study was run on three groups of hospitalised 40 patients with medium to serious lung TB to evaluate the effectiveness of generic liver protector drugs, UDPG, and an association of UDPG-GSH in the prevention a nd hindrance of organic and metabolic-functional liver alterations in the course of chemotherapy. It was found that UDPG--particularly in association with GSH--gave highly significant results by comparison with generic protector drugs.

[Evaluation of the changes in some laboratory parameters in liver disease patients treated with Toxepasi Complex]. / Valutazione delle modificazioni di alcuni parametri di laboratorio in epato-pazienti sottoposti a trattamento con Toxepasi Complex

Toxepasi Complex (UDPG, glutathione and vitamin B12) was administered to patients with aggressive chronic hepatitis and a second group with severe cirrhosis. Changes in laboratory enzymological data indicative of the overall extent of liver damage due to cell necrosis, cholostasis and impairment of protein synthesis were evaluated. Decreases tending to normalisation were noted two weeks after the commencement of treatment, particularly in the first group. The results suggest that the complex may be usefully employed in the management of aggressive chronic hepatitis and cirrhosis of the liver.

[Clinical studies of the effect of a phosphorylated glycoderivative in acute viral hepatitis]. / Ricerca clinica sull'effetto di un glicoderivato fosforilato nell'epatite acuta da virus

Experimentation of two i.v. doses of a uridine-5-diphosphoglucose (UDPG) in 30 cases of acute viral hepatitis is reported. The therapeutic efficacy of the drug was assessed on qualitative and quantitative parameters indicative of liver distress. Statistically significant evidence was obtained of the efficacy of UDPG in acute and serious liver disease, and of the greater effectiveness of one of the two doses used. Excellent local and general tolerance was noted.

Comparison of treatments for congenital nonobstructive nonhaemolytic hyperbilirubinaemia.

A patient with Crigler-Najjar disease has survived with the help of phototherapy to the age of 2 years without neurological damage. Because long periods of phototherapy are a threat to normal development, a search was made for supplementary treatments. Cholestyramine and a high fat diet were effective, and possibly also aspartic acid. Maintenance therapy with cholestyramine allowed the amount of phototherapy given to be reduced.