Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

Lymphatic transport of salicylates in dogs.

1. Pharmacokinetic parameters were determined for acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma and lymph following the intravenous or oral administration of a water-soluble preparation of lysine-acetylsalicylic acid to dogs. 2. By both routes of administration, ASA but not SA, tended to be deposited in lymph, as indicated by the ratio between the area under the concentration-time curve constructed for the parent compound and its metabolite in lymph and plasma. 3. A reduced conversion of ASA to SA by esterases in lymph, and lymphatic absorption of ASA following the oral administration might be factors responsible for the accumulation of the compound in the lymphatic system. 4. It is suggested that the lymphatic system might serve as a temporary reservoir compartment for ASA.

Effect of praseodymium chloride on liver microsomal enzymes of rats.

A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium.

Effects of ethanol on experimental inflammation.

The carrageenin and nystatin-induced paw edemas were dose-dependently antagonized by oral administration of ethanol. The combination of ethanol and dexamethasone increased this inhibition. Carrageenin-induced edema was also inhibited by furosemide and pentobarbital. The vascular permeability effects of histamine and serotonin were markedly suppressed by ethanol pretreatment. However, ethanol was unable to suppress the granuloma formation caused by cotton pellet implantation. These results suggest that central depression, cardiovascular alteration and decreased vascular permeability may play an important role for ethanol antiinflammatory activity.

Some characteristics of acute inflammation induced by econazole.

Aqueous suspension of econazole nitrate injected into subplantar region of rat foot induces a sharp and long-lasting inflammation. The econazole-induced edema is characterized by the existence of two phases of accelerated evolution, with peak values at 2nd and 12th hr after injection. Only the second phase of econazole-induced edema is selectively inhibited by either steroidal or non-steroidal anti-inflammatory drugs.

Linfocitos e biotransformacao de drogas. / lymphocytes and biotransformation of drugs

Os autores apresentam alguns aspectos da biotransformacao de drogas, relatanto particularmente sobre as propriedades de aril-hidrocarboneto hidroxilase (AHH) linfocitaria que e uma das enzimas constituintes do sistema oxigenase de funcao mista dos microssomas. As prespectivas quanto a aplicacao da cultura de linfocitos humanos como modelo experimental, para o diagnostico de neoplasias e os problemas metodologicos sao relatados

Effects of isoproterenol on the toxicity in rats of compounds eliminated by the kidneys.

In rats, l-isoproterenol (0.3 mg kg-1 s.c.) reduced the "average total body clearance" (as measured by dose/AUC) and the LD50 of various compounds that are eliminated almost entirely by the kidneys. These effects involve beta-adrenergic receptors since they are blocked by propranolol. Propranolol pretreatment prevented the isoproterenol-induced decreases in renal clearances of methoxy-inulin and tetraethylammonium bromide. Treatment with the alpha-adrenergic-blocking agent, phentolamine, potentiated the decreses in the renal clearances of these substances. The effects of isoproterenol were as marked in hypophysectomized as in intact rats. Peak plasma levels of isoproterenol after subcutaneous administration (0.3 mg kg-1) were about 42 ng ml-1.

Antiarrhythmic effect of solvents: propylene glycol, benzyl alcohol.

Propylene glycol and benzyl alcohol, the main constituents of most solvent vehicles, display a pronounced antiarrhythmic-antifibrillatory effects, when injected intravenously into animals (dogs, rats) with spontaneous or drug-induced arrhythmias. The antiarrhythmic dose for propylene glycol amounts to 0.2-0.3 ml/kg of a 70 per cent solution and, for benzyl alcohol to 0.2-0.4 ml/kg of a 4 per cent solution in physiologic saline, respectively. Similar effects were also obtained by the combined injection of propylene glycol + benzyl alcohol, in proportions which correspond to the formulae of numerous commercial "solvents" (vehicles): 2 to 20 per cent solutions of benzyl alcohol in 70 per cent propylene glycol (0.05-0.2 ml/kg). The mechanisms which might be responsible for the antiarrhythmic activity of solvents are discussed: lengthening of the effective refractory period, local and general anaesthetic effects, changes of osmolarity. The intravenous injection of propylene glycol and/or benzyl alcohol, in high doses, produces intravascular haemolysis. Clinical investigations are recommended as to the potential, beneficial or toxic effects of drug solvents, especially upon the cardiocirculatory system.