Hepatotoxicidad de rizatriptán. Descripción de un caso clínico

Fernández-Atutxa, Alberto; Vergara, Mercedes; Gil, Montserrat; Dalmau, Blai; Miquel, Mireia; Sánchez-Delgado, Jordi; Casas, Meritxell

doi:10.1016/j.gastrohep.2012.07.010

Cited by 4 publications

(4 citation statements)

References 9 publications

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“…Surprisingly 42 cases of all of the patients were children [1]. Previously, some adverse effects of triptans including harmful effects on the kidneys and liver have been described [2][3][4][5]. Larivière and colleagues reviewed data collected by the Lille poison center between 2000 and 2009 regarding cases of acute triptan poisoning in children younger than 6 years and reported 84 patients suffering from triptans toxicity [6].…”

Section: Introduction ▼mentioning

confidence: 99%

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Triazole rizatriptan Induces Liver Toxicity through Lysosomal/Mitochondrial Dysfunction

et al. 2016

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Triptans are used as antimigraine agents. Some cases of hepatotoxicity by triptans have been reported. However, the exact mechanism of triptan-induced hepatotoxicity is not clear yet. In this study, the cytotoxic effects of rizatriptan were investigated in freshly isolated rat hepatocytes using accelerated cytotoxicity mechanism screening. We designed experiments to evaluate toxicity markers, such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, lysosomal membrane integrity and the amount of reduced and oxidized glutathione in the rizatriptan-treated hepatocytes. Cytotoxicity caused by rizatriptan in rat hepatocytes was concentration-dependent. An increase in ROS formation accompanied by a significant rise in lipid peroxidation, mitochondrial depolarization and loss of lysosomal membrane integrity was observed. Cellular glutathione reservoirs were decreased and a significant amount of oxidized glutathione was formed. All the aforementioned rizatriptan-induced cellular events were significantly (p<0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Also, the present results demonstrated that CYP450 is involved in rizatriptan-induced oxidative stress and cytotoxicity mechanism and different CYP450 inducers had different effects on the toxicity. It is suggested that the adverse effect of rizatriptan towards hepatocytes is mediated by oxidative stress and the hepatocytes lysosomes and mitochondria play an important role in rizatriptan-induced cell injury.

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Section: Introduction ▼mentioning

confidence: 99%

“…Rizatriptan administration as an antimigraine drug has been associated with toxic effects on several organs such as liver and kidney [2][3][4][5]. In addition, oxidative stress is known to be one of the major reasons causing migraine [50] and likewise, the ROS formation is also increased during migraine attack [51].…”

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confidence: 99%

Triazole rizatriptan Induces Liver Toxicity through Lysosomal/Mitochondrial Dysfunction

et al. 2016

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“…Several organs such as liver are involved in triptans adverse effects. [15][16][17] It is well known that imbalance between antioxidant defense and ROS generation (e.g., glutathione) to removal of ROS lead to oxidative stress. 49 GSH is an important antioxidant defense molecule for removal of reactive oxygen species such as lipid hydroperoxides and H 2 O 2 .…”

Section: Lipid Peroxides Productionmentioning

confidence: 99%

“…14,15 Most recent toxic effects of triptans on liver and the cases of hepatotoxicity of triptans have been reported. 16 Another case report was a 17-year-old girl who developed hepatotoxicity during treatment with antimigraine triptans. 17 Sumatriptan is in the possible hepatotoxic class of drugs according to its structural moiety.…”

Section: Introductionmentioning

confidence: 99%