Effects of dibenzothioline and silymarin on the dry weight of isolated hepatocytes of rats acutely poisoned with phalloidin and alpha-amanitin.

The protective action of dibenzothioline and silymarin in the acute intoxication by phalloidin and alpha-amanitin has been studied on the basis of their ability to attenuate changes in dry mass distribution and class-pattern of the hepatocytes, as evaluated by microinterferometry. Protective agents were given to male rats 30 min before toxin, and the animals were sacrificed 3.0 h later.

[Effect of silymarin on the total dry mass of hepatocytes inacute poisoning by phalloidin and alpha-amanitine (author's transl)].

The effects of silymarin on the total dry mass and class pattern of rat hepatocytes have been studied during acute poisoning by phalloidin and alpha-amanitine. Phalloidin (2/5 of the LD50) after 3 h causes a marked change in the hepatocyte class pattern due to a displacement of a high percentage of cells in the intervals among classes, while the cell dry mass increases slightly. alpha-Amanitine (1/4 or 1/2 of the LD50) after 3 h causes a decrease in the number of classes of hepatocytes due to a disappearance of the heavier ones, a displacement of cells in the intervals among classes, an appearance of very light cells, and a decrease by about 25% in the mean dry mass of the hepatocytes.

Conformational effects on the activity of drugs. 5. Pharmacological properties of 2-(p-nitrophenyl)-4-isopropylmorpholine, a cyclic analog of INPEA.

2-(p-Nitrophenyl)-4-isopropylmorphine (V), an analog of 1-(p-nitrophenyl)-2-isopropylaminoethanol (INPEA, I) in which the OCHCHN chain of I is locked in a morpholine ring, loses the beta-receptor blocking activity of I on various isolated preparations. The same ineffectiveness is observed in the O-methyl (II), N-methyl (III), and N,O-dimethyl analog (IV) of I. However, some other properties which are present in I, such as inhibitory effect on acetylcholine or on 5-HT, intrinsic alpha-sympathomimetic activity, and potentiation of catecholamines, are maintained; this demonstrates a complete dissociation of these effects from beta-receptor blockade.