Al2O3 nanoparticles trigger the embryonic hepatotoxic response and potentiate TNF-α-induced apoptosis-modulatory effect of p38 MAPK and JNK inhibitors

Recent evidences illustrated that the release of aluminum oxide nanoparticles (Al2O3-NPs) into the biosphere may pose risk to the environment and cause adverse effects on living organisms including humans. The current study assessed the hepatotoxic effects of Al2O3-NPs on developing chicken embryo and cell culture models. Results demonstrated that Al2O3-NPs exposure causes histological abnormalities and increased the level of tissue damage markers (ALP, AST, and ALT) in the embryonic liver. Furthermore, increased oxidative stress (TBARS) and impaired function of antioxidant enzymes (SOD, CAT, and GPx) were also observed. Moreover, it adversely affects red blood cells (RBC) morphology, liver metabolism, and stress response gene expression (HO-1 and NQO-1). Dose-dependent ROS generation and cytotoxic response in addition to potentiating effect on tumor necrosis factor alpha (TNF-alpha)-induced apoptosis (caspase-3 activity) were also observed. Inhibition of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) pathways modulates Al2O3-NPs-induced apoptosis in HepG2 cells. Novel mechanisms behind embryonic hepatotoxicity, cytotoxic potentiating effects, and possible prevention strategies have been explored.

Automated summary

Recent evidences have shown that the release of aluminum oxide nanoparticles (Al2O3-NPs) may pose a risk to the environment and cause adverse effects on living organisms. This study investigated the hepatotoxic effects of Al2O3-NPs on developing chicken embryos and cell cultures. The results revealed that exposure to Al2O3-NPs caused abnormal liver histology, increased tissue damage markers, oxidative stress, impaired antioxidant enzyme function, abnormal red blood cell morphology, and enhanced apoptosis. Additionally, novel mechanisms and prevention strategies were explored.