Recreational MDMA doses do not elicit hepatotoxicity in HepG2 spheroids under normo- and hyperthermia.

MDMA (3,4-methylenedioxymethamphetamine), an entactogen with empathogenic and prosocial effects, is widely used in music festivals and other festive settings. High MDMA doses have been associated with drug-induced liver injury and cases of hyperthermia. Although the latter condition is thought to increase MDMA hepatotoxicity, this correlation remains poorly explored for recreational MDMA doses. On the other hand, the fact that MDMA acts to extinguish fear and to reconsolidate memory could be explored as an adjunct to psychotherapy during treatment of neuropsychiatric disorders such as post-traumatic stress disorder. In this context, assessing MDMA toxicity is relevant, and tridimensional cell culture has emerged as an alternative to animal models in toxicity assessment. Herein, we have used HepG2 spheroids to evaluate MDMA-induced hepatotoxicity at recreational doses, under normo- or hyperthermia. The MTT reduction assay did not evidence significantly reduced cell viability. Moreover, MDMA did not increase reactive oxygen species production, deplete the mitochondrial membrane potential, arrest the cell cycle, or induce apoptotic cell death. These findings support further pre-clinical investigation of MDMA safety from the perspective of both harm reduction and therapy given that non-abusive recreational and therapeutic doses overlap.

Targeting Oxidative Stress with Polyphenols to Fight Liver Diseases.

Reactive oxygen species (ROS) are important second messengers in many metabolic processes and signaling pathways. Disruption of the balance between ROS generation and antioxidant defenses results in the overproduction of ROS and subsequent oxidative damage to biomolecules and cellular components that disturb cellular function. Oxidative stress contributes to the initiation and progression of many liver pathologies such as ischemia-reperfusion injury (LIRI), non-alcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Therefore, controlling ROS production is an attractive therapeutic strategy in relation to their treatment. In recent years, increasing evidence has supported the therapeutic effects of polyphenols on liver injury via the regulation of ROS levels. In the current review, we summarize the effects of polyphenols, such as quercetin, resveratrol, and curcumin, on oxidative damage during conditions that induce liver injury, such as LIRI, NAFLD, and HCC.

Surface facet Fe2O3-based visible light photocatalytic activation of persulfate for the removal of RR120 dye: nonlinear modeling and optimization.

Photocatalytic activation of persulfate (PS) is recently emerged as an energy-efficient and environmentally sustainable approach for pollutants degradation, which enables to leverage the strengths of low-cost solar energy and heterogeneous catalysis. Herein, we investigated the photocatalytic decomposition of reactive red 120 (RR120) dye using PS-activated Fe2O3 nanoparticles and elucidated the effect of their facets, α-Fe2O3 (001), ß-Fe2O3 (100), and γ-Fe2O3 (111). ß-Fe2O3 not only boosted the charge carrier separation but also provided more active sites for PS activation resulting in 6- and 3.5-fold higher photocatalytic activities compared to α-Fe2O3 and γ-Fe2O3, respectively. Response surface methodology and artificial neural network coupled with genetic algorithm models were utilized to optimize and foresee Fe2O3/PS system under visible light. Almost 100% color removal and 82% organic removal were observed under the optimum conditions at 20 mg/L RR120, 22 mg/L ß-Fe2O3, 18 mg/L PS, and pH: 3. Scavenger test indicated that both sulfate and hydroxyl radicals are responsible for the observed RR120 removal. Although cell viability test indicated that cytotoxicity of wastewater is not significantly reduced after treatment. All the results proposed that ß-Fe2O3/PS at relatively low doses has a great potential to decompose and mineralize recalcitrant dyes in wastewater under invisible light.