Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats.

The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause a significant reduction in plasma lipid levels. Daily administration of a 10% (w/w) OFS-containing diet to normolipidemic male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect was observed after one week and lasted for at least 16 wk and was associated with a reduction in plasma very low density lipoproteins, indicating that the hypolipidemic effect of OFS may be due to changes in liver lipid metabolism.

Toxicity of the antitumoral drug datelliptium in hepatic cells: Use of models in vitro for the prediction of toxicity in vivo.

Datelliptium is a DNA-intercalating agent derived from ellipticine. The drug has potent antitumoral activity in vitro and in vivo. The first clinical use of the drug revealed unexpected hepatotoxic effects in humans that had not been observed in animals.

Biochemical effects of methotrexate in isolated hepatocytes in relation to its steatogenic activity.

Methotrexate (MTX) is known to induce steatosis in humans. The effect of MTX on the synthesis and secretion of triglycerides and proteins as well as on RNA synthesis were evaluated using isolated rat hepatocytes in suspension as an experimental model. MTX significantly inhibited protein synthesis (48% inhibition after 180 min) and RNA synthesis (72% inhibition after 180 min) at 10(-3)m but not at a concentration of 10(-4)m.

Adult rat liver slices as a model for studying the hepatotoxicity of vincaalkaloids.

There are certain disadvantages associated with the use of isolated or cultured cells including the need to use proteolytic enzymes for their isolation and loss of tissue organization. In order to provide an in vitro system for toxicological studies that preserves tissue integrity, a method for preparation and incubation of adult rat liver slices has been developed. Fresh ultra-thin liver slices were produced in large quantities at a rapid rate under conditions that cause minimal tissue trauma.

Investigation into the mechanism of tetracycline-induced steatosis: study in isolated hepatocytes.

Tetracycline is known to cause hepatic dysfunction in humans by inducing steatosis. Accumulation of fat in the liver could result from biochemical effects at various levels in the sequence from protein and triglyceride synthesis to lipoprotein secretion. The effects of tetracycline on the synthesis and secretion of triglycerides and proteins were studied in isolated rat hepatocytes surviving in suspension for up to 2.

Critical biochemical functions of isolated hepatocytes as sensitive indicators of chemical toxicity.

Isolated hepatocytes from adult male Wistar rats are a suitable experimental model to study the cytotoxicity of chemicals. Indeed, the isolated cells incubated in suspension in a Waymouth medium supplemented with 10% newborn calf serum maintain critical biochemical functions such as cytochrome P-450-dependent monooxygenase activity, glycogen, and protein synthesis capacities. This cellular model is used to detect the early biochemical effects of various xenobiotics, i.

Effects of diethyl maleate on protein synthesis in isolated hepatocytes.

Diethyl maleate is commonly used in toxicological and drug metabolism research using isolated adult rat hepatocytes. At the highest concentrations used the effect of diethyl maleate is, however, not limited to glutathione depletion. In these conditions it inhibits protein synthesis and it impairs the "L" system for amino acid transport.

Biochemical effects of nitrosopyrrolidine on isolated hepatocytes.

The present communication reports the effects of N-nitroso-pyrrolidine (NPYR) on some essential metabolic pathways in isolated hepatocytes. Isolated cells prepared by the collagenase-perfusion technique are incubated for 4 hours in suspension in a Waymouth medium, either in the absence or in the presence of NPYR (20 to 40 mmol/l). Under these conditions, NPYR, even at 40 mmol/l, has no effect on the vital staining of the cells by erythrosin B and does not increase the leakage of LDH, indicating no lethal effect.

Interference of chemicals with glycogen metabolism in isolated hepatocytes.

Freshly isolated hepatocytes in suspension were used to evaluate the possible effects of certain chemicals. Conditions including the choice of the incubation medium have been defined for maintaining the cells competent for a sufficient length of time. Using paracetamol alone or in combination with diethylmaleate, we have been able to show that these chemicals markedly alter the metabolic state of the cells, as indicated by an inhibition of glycogen synthesis and even by an enhancement of glycogen degradation, without modifying membrane integrity.