Biosynthesis of digitalis-like compounds in rat adrenal cells: hydroxycholesterol as possible precursor.

The biosynthesis of digitalis-like compounds (DLC) was determined in bovine and rat adrenal homogenates, as well as in primary rat adrenal cells, by following changes in the concentration of DLC using three independent sensitive bioassays: inhibition of [3H]-ouabain binding to red blood cells and competitive ouabain and bufalin ELISA. The amounts of DLC in bovine and rat adrenal homogenates, as measured by the two first bioassays, increased with time when the mixtures were incubated under tissue culture conditions. Rat primary adrenal cells were incubated in the presence of [1,2-(3)H]-25-hydroxycholesterol, [26,27-(3)H]-25-hydroxycholesterol or [7-(3)H]-pregnenolone. The radioactive products, as well as the digitalis-like activity, were fractionated by three sequential chromatography systems. When [1,2-(3)H]-25-hydroxycholesterol or [7-(3)H]-pregnenolone was added to the culture medium, the radioactivity was co-eluted with digitalis-like activity, suggesting that at least one of the DLC might originate in hydroxycholesterol. In contrast, when the culture medium was supplemented with [26,27-(3)H]-25-hydroxycholesterol, the radioactivity was not co-eluted with the digitalis-like activity, indicating that side chain cleavage is the first step in the synthesis of digitalis-like compounds by rat adrenal.

Intoxicaçäo digitálica / Digitalis intoxication

O fator mais importante na intoxicaçäo digitálica é o seu reconhecimento. A intoxicaçäo continua sendo comum e de difícil confirmaçao. Isto se deve às semelhanças existentes entre arritmias, sintomas geraos pela intoxicaçäo digitálica e doença cardíaca de base. Além disso, os níveis plasmáticos terapêuticos da digoxina apresentam alto grau de variabilidade e muitas vezes sobrepöm-se aos da toxicidade, näo servindo, portanto, como parâmetro diagnóstico, especialmente na emergência. A intoxicaçäo pela digital, complicaçäo potencialmente fatal, inclui também os pacientes que ingerem doses maciças na medicaçäo intencional ou acidentalmente. A terapia convencional continua sendo a reposiçäo de potássio sempre que necessário, objetivando manter nível plasmático igual ou superior a 4 mEq/l, o controle dos níveis do magnésio e cálcio, correçäo do balanço hídrico e ácido-básico, bem como a adminstraçäo de antiarrítmicos apropriados ou a instalaçäo de marcapasso temporário. A aquisiçäo terapêutica mais recente é o uso de anticorpo antidigoxina (Fab), que apesar do seu alto custo, quando bem indicado, constitui tratamento efetivo. O objetivo deste artigo é rever o mecanismo de açäo da digital, realçar as manifestaçöes cardíacas e extracardíacas da intoxicaçäo, rever a importância da determinaçäo dos níveis séricos da digital e as alternativas terapêuticas.

Progesterone: its possible role in the biosynthesis of cardenolides in Digitalis lanata.

The incorporation of progestrone-7alpha-(3)H and pregnenolone-7alpha-(3)H into digitoxigenin, gitoxigenin, and digoxigenin in isolated, surviving leaves of Digitalis lanata was demonstrated. In addition, the conversion of pregnenolone to progesterone in the same system was proved. The results tend to indicate that progesterone is as good a precursor of cardenolides as pregnenolone It is suggested that the biosynthesis of cardenolides might proceed through the intermediacy of progesterone.