[Mechanism of cellular toxicity induced by digitalis compounds. Study with ouabain].
The toxic effect of digitalis compounds at cell level produces an intracellular Ca2+ overload and a decrease in intracellular concentrations of K+. Since Ca2+ and K+ are critical modulators of life and death, the purpose of this study was to explore the cell death pathway activated through the ionic imbalance provoked by digitalis intoxication. We present results of cell toxicity in a study performed with ouabain acting on a HeLa cells culture and on guinea pig heart myocites under ouabain intoxication.


RESULTS
In tissue culture, ouabain produced inhibition of cell viability in a time and dose dependent manner. Through ethidium-bromide staining, nuclear condensation and fragmentation were observed. The electrophoretic analysis of nuclear DNA in agarose gel showed a degradation pattern characteristic of apoptosis. In histologic sections of guinea pig heart under ouabain intoxication (50-60% of lethal doses), in situ cell death was detected by in situ DNA TUNEL labeling. We conclude that the electrical and physiologic imbalance produced by toxic doses of ouabain activates mechanisms that cause cell death via apoptosis in heart myocites and fast growing cells.
Ramírez Ortega
Margarita del C
Mdel C
Departamento de Farmacología, Instituto Nacional de Cardiología Ignacio Chávez, INCICH, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 14080 México, D. F. margarita0022@yahoo.com
Maldonado Lagunas
Vilma
V
Meléndez Zajgla
Jorge
J
Zarco Olvera
Gabriela
G
Avila Casados
Ma Del Carmen
Mdel C
Suárez Munguía
Jorge
J
Pastelín Hernández
Gustavo
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D006168:Guinea Pigs; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010042:Ouabain / Q000633:toxicity*
D002316:Cardiotonic Agents; D010042:Ouabain