Abstract
In female rats, the lethality and hepatotoxicity of cerous chloride (CeCl3) were significantly altered by pretreatment with steroidal and nonsteroidal compounds (pregnenolone-16α-carbonitrile “PCN”, dexamethasone, spironolactone, phenobarbital) that stimulate hepatic drug-metabolizing enzyme activity and by estradiol. PCN, estradiol, and dexamethasone considerably decreased hepatic triglycerides, but the latter steroid also greatly sensitized the animals to CeCl3 lethality. Spironolactone and phenobarbital similarly lowered the triglyceride level but not significantly. Light and electron microscopy indicated that the hepatocytic damage elicited by CeCl3 was decreased significantly by PCN, estradiol, and dexamethasone. The steroids may have altered the distribution and binding of the metal to the endoplasmic reticulum (ER) thus protecting these membranes against the effect of cerium.
Zusammenfassung
Nach Vorbehandlung mit Steroiden und mit nicht steroidartigen Substanzen (Pregnenolon-16α-carbonitril „PCN“, Dexamethason, Spironolacton, Phenobarbital), welche die arzneimittelmetabolisierenden Enzyme der Leber stimulieren, und nach Oestradiol, wurde die Sterblichkeit und die Lebertoxicität der weiblichen Ratte erheblich verändert. PCN, Oestradiol, Dexamethason senken die hepatischen Triglyceride wesentlich, jedoch erhöht Dexamethason die Sensitivität der Tiere für CeCl3 bedeutend. Spironolacton und Phenobarbital üben keine große Wirkung auf die Triglyceride aus. Licht- und Elektronenmikroskopie zeigten, daß die durch CeCl3 hervorgerufenen hepatocellulären Veränderungen durch PCN, Oestradiol und Dexamethason bedeutend verringert wurden. Die Steroide dürften die Verteilung und die Bindung des Metalles an das endoplasmatische Reticulum verändern, und somit diese Membranen vor Cerium schützen.
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Part of this work appeared in abstract form (Salas et al., 1974) and in an M.Sc. Thesis (Salas, 1973).
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Salas, M., Tuchweber, B. Prevention by steroids of cerium hepatotoxicity. Arch Toxicol 35, 115–125 (1976). https://doi.org/10.1007/BF00372765
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DOI: https://doi.org/10.1007/BF00372765
Key words
- Cerium
- Microsomal enzyme inducers
- Pregnenolone-16α-car-bonitrile
- Estradiol
- Fatty liver
- Ultrastructure
- Triglycerides