Neurotoxicity of some MAO inhibitors in adult rat hypothalamic cell culture

Hurtado-Guzmán, Claudio; Martinez-Alvarado, Pedro; Dagnino‐Subiabre, Alexies; Paris, Irmgard; Caviedes, Pablo; Caviedes, Raúl; Cassets, B. K.; Segura‐Aguilar, Juan

doi:10.1080/10298420290015944

Cited by 7 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Former studies have shown that repression of neuronal-specific genes by CoREST required the participation of LSD1 ( 43 ). MAO inhibitors were found to be neurotoxic in a concentration-dependent manner in adult rat hypothalamic cell culture ( 26 ). And tranylcypromine treatment also showed CNS side effects in clinical therapies ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

et al. 2017

View full text Add to dashboard Cite

Recent breakthroughs in human pluripotent stem cell-derived cerebral organoids provide a valuable platform for investigating the human brain after different drugs treatments and for understanding the complex genetic background to human pathology. Here, we identified tranylcypromine, which is used to treat refractory depression, caused human-induced pluripotent stem cell-derived brain organoids neurotoxicity, leading to decreased proliferation activity and apoptosis induction. Moreover, tranylcypromine treatment affects neurons and astrocytes, which impairs cell density and arrangement. Finally, staining of histone demethylation-related genes revealed that tranylcypromine suppresses the transcriptional activity of BHC110/LSD1-targeted genes and increases the expression of histone di-methylated K4. These results show that human brain organoids can be applied as an in vitro model for CNS drug screening to evaluate structural, cellular, and molecular changes in the normal brains or brains of patients with neuropsychiatric disorders after drug treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The RCHT cell line was derived from the hypothalamus of a 4 month old normal Fisher 344 rat. The RCHT cell line grows in monolayers, with a doubling time of 52 h, a plating efficiency of 21%, and a saturation density of 56.000 cells/cm 2 when kept in normal growth media composed of DME/HAM-F12 (1:1), 10% bovine serum, 2.5% fetal bovine serum, and 40 mg/L gentamicine sulfate (20). The cultures were kept in an incubator at 37 °C with 100% humidity and an atmosphere of 10% CO2.…”

Section: Methodsmentioning

confidence: 99%

Dopamine-Dependent Iron Toxicity in Cells Derived from Rat Hypothalamus

Paris

Martinez-Alvarado

Cárdenas

et al. 2005

Chem. Res. Toxicol.

View full text Add to dashboard Cite

We report a new and specific mechanism for iron-mediated neurotoxicity using RCHT cells, which were derived from rat hypothalamus. RCHT cells exhibit immunofluorescent-positive markers for dopamine beta-hydroxylase and the norepinephrine transporter, NET. In the present study, we observed that iron-induced neurotoxicity in RCHT cells was dependent on (i) formation of an Fe-dopamine complex (100 microM FeCl3:100 microM dopamine); (ii) specific uptake of the Fe-dopamine complex into RCHT cells via NET (79+/-2 pmol 59Fe/mg/min; P<0.05), since the uptake of the 59Fe-dopamine complex by the cells was inhibited by 30 microM reboxetine, a specific NET inhibitor (78% inhibition, P<0.001); and (iii) intracellular oxidation of dopamine present in the Fe-dopamine complex to aminochrome; (iv) inhibition of DT-diaphorase, since incubation of RCHT cells with 100 microM Fe-dopamine complex in the presence of 100 microM dicoumarol, an inhibitor of DT-diaphorase, induced significant cell death (51+/-5%; P<0.001). However, this cell death was reduced by 75% when the cells were incubated in the presence of 30 microM reboxetine (P<0.01). No significant cell death was observed when the cells were incubated with 100 microM dopamine, 100 microM Fe-Dopamine complex, 100 microM dicoumarol, or 100 microM FeCl3 (8.3+/-2, 9+/-4, 8.5+/-3, or 9.7+/-2% of control, respectively). ESR studies using the spin trapping agent DMPO showed no formation of hydroxyl radicals when the cells were incubated with 100 microM FeCl3 alone. However, using the same ESR technique, the formation of hydroxyl radicals and a carbon-centered radical was detected when the cells were incubated with 100 microM Fe-dopamine complex in the presence of 100 microM dicoumarol. These studies suggest that iron can induce cell toxicity by a mechanism that requires the formation and NET-mediated uptake of an Fe-dopamine complex, ultimately resulting in the intracellular formation of reactive species.

show abstract

“…In vitro studies showed that MTA induces neurotoxicity in rat hypothalamic culture cells (Hurtado-Guzmán et al, 2002), and in vivo studies showed that MTA induces hyperthermia in mice, another potentially lethal consequence of amphetamine intoxications (Carmo et al, 2003). The only evidence that MTA induced hepatotoxicity, and that this is mediated through its effect on mitochondria, comes from the observation that high MTA concentrations (1 mM) significantly reduced the ATP content in primary hepatocytes isolated from different animal species, namely human, monkey, dog, rabbit, rat and mouse (Carmo et al, 2004).…”

Section: Introductionmentioning

confidence: 99%