The potential toxic effects of magnesium oxide nanoparticles and valproate on liver tissue

Abstract

The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid‐coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three‐dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)‐induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues.

Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles

“…In order to investigate the effect of nanomaterials on the liver, a 3D liver model with liver-specific functions must be created in vitro . Several studies have been reported on the effects of nanomaterials on 3D liver models [ 30 , 42 , 43 , 44 , 45 ]. Kermanizadeh A. et al evaluated the hepatotoxicity of human liver cell heterospheroids by various nanomaterials (Ag, ZnO, MWCNT, and a positively charged TiO 2 ) [ 42 ].…”

“…Kermanizadeh A. et al evaluated the hepatotoxicity of human liver cell heterospheroids by various nanomaterials (Ag, ZnO, MWCNT, and a positively charged TiO 2 ) [ 42 ]. Mekky G. et al reported on the effects of magnesium oxide nanoparticles using primary human liver cell heterospheroids and animals [ 43 ]. Tee J.K. et al reported on the effects of TiO 2 nanoparticles using LO2 cell–sinusoidal endothelial cell heterospheroids [ 44 ].…”

“…Fleddermann J. et al reported on the distribution of SiO 2 nanoparticles in HepG2 cell monospheroids [ 45 ]. Various types of nanoparticles can be evaluated for liver functions in 3D liver models [ 30 , 42 , 43 , 44 , 45 ], and the obtained results can support in vivo [ 43 ]. In our previous reports, the heterospheroids of endothelial cells and primary hepatocytes exhibited liver-like structures, and maintained the albumin secretory capacity, CYP3A activity, and glucuronidation for an extended period [ 4 , 5 ].…”

Application Progress of Organoids in Colorectal Cancer

“…Human liver organoids were used to test the toxicity of aspartic acid-coated magnesium oxide nanoparticles and valproate. These two drugs have toxic effects on the liver organoids by reducing cell viability, reducing ATP, and increasing reactive oxygen species ( Mekky et al, 2021 ). Liver organoids were applied to verify the toxicity of drugs that had been withdrawn from the market due to hepatotoxicity, such as troglitazone, trovafloxacin.…”

The mechanistic effects of human digestion on magnesium oxide nanoparticles: implications for probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium bifidum VPI 1124

“…14 Gelli et al (2015) highlighted the pulmonary toxicity that MgO-NPs produced in rats, and Mekky and coworkers (2021) revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels suggesting potential toxic effects of nano Mg on the liver tissue samples of a rat convulsion model. 15,16 In vitro, contradictory results have been reported about the toxicity of MgO-NPs. While some authors described that exposure of various mammalian cell lines to MgO-NPs led to cytotoxic effects, such as reduced cell viability, mitochondrial and lysosomal malfunctions, DNA damage, oxidative stress, and apoptosis, Mittag et al (2019) indicated that MgO-NPs had no cytotoxic or genotoxic effects in intestinal HT29 cells and did not induce apoptosis, cell cycle changes, or oxidative stress.…”