Comparison of Dantrolene Sodium with Erythromycin Estolate Using Primary Cultures of Rat Hepatocytes

Abstract

Using primary cultures of parenchymal hepatocytes as a model system, the cytotoxic potential of dantrolene sodium (DS) was compared with that of erythromycin estolate (EE)--a known hepatotoxin. Parallel morphological and functional comparisons were made, following 4-, 8-, or 24-h exposures of hepatocyte cultures, using phase contrast microscopy and lactate dehydrogenase (LDH) leakage, respectively. Four-hour exposures of cultures to rather low concentrations of EE (i.e. 50 microM) resulted in cellular necrosis and significantly elevated LDH release. As the concentration of this hepatotoxin was increased, the changes were more pronounced. However, even 4- or 8-h exposures of cultures to a maximum of 100 microM DS did not affect LDH leakage or morphological integrity, although marginally detectable morphological changes did not occur at the highest concentration after 24-h. The value of using primary parenchymal hepatocyte cultures as a model system for the assessment of xenobiotic-induced hepatotoxicity was confirmed.

Dantrolene: Mechanisms of Neuroprotection and Possible Clinical Applications in the Neurointensive Care Unit

“…In fact, dantrolene is hepato-protective in an in vivo rat model of liver injury 27. In a hepatocyte culture model, dantrolene did not produce any hepatotoxicity 28.…”

Current and prospective sights in mechanism of deoxynivalenol‐induced emesis for future scientific study and clinical treatment

“…It achieves this ability by inhibiting Ca 2+ ions release from sarcoplasmic reticulum stores by antagonizing RyRs. This chemical drug can induce different side effects in the central nervous system (visual disturbances, mental depression and confusion) and liver (liver inflammation) (Krause et al , ; Sorensen & Acosta, ). These data indicate that palonosetron and dantrolene have the potential adverse effects in humans.…”

Malignant Hyperthermia in Liver Transplantation

“…Despite these facts, a few authors suggest that other concomitant therapies may have had a role in that toxicity [75][76] . In addition, in vivo experiments in mice have not revealed any toxicity to hepatocytes [85][86] . In fact, recently, it was argued that dantrolene, due to its properties of restoring calcium homeostasis in scenarios of its disruption (like models of ischemia, hypoxia, seizure, trauma, anesthesia, and neurodegenerative diseases), may have cytoprotective effects in different tissue culture or animal models of diseases involving cytotoxicity induced by disruption of intracellular calcium homeostasis in pathogenesis 87 .…”