# Response to Oxidative Stress Induced by Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine in Differentiated PC12 Cells

## TL;DR

This study explores how HMX, a common explosive material, causes toxicity in nerve-like cells by increasing oxidative stress and disrupting calcium and brain signaling.

## Contribution

The study reveals novel molecular mechanisms of HMX-induced neurotoxicity involving oxidative stress and altered signaling pathways in PC12 cells.

## Key findings

- HMX reduced cell viability and increased intracellular calcium levels in PC12 cells.
- HMX induced oxidative stress, as shown by elevated ROS and MDA levels and mitochondrial membrane potential loss.
- HMX altered BDNF and iGluRs expression and disrupted gene transcription in PC12 cells.

## Abstract

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a globally recognized energetic material that widely used in industrial, mining, and military fields. Like hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and other nitramine compounds, HMX has also been reported to exhibit neurotoxicity. However, the molecular mechanisms underlying the toxic effects of HMX remain poorly understood. Therefore, this study aims to investigate the neurotoxicity induced by HMX by adopting PC12 cells. The results show that HMX treatment decreased cell viability and upregulated the intracellular free calcium ions (Ca2+) in PC12 cells. Furthermore, HMX caused aggravated oxidative stress in PC12 cells, as evidenced by the upregulations of reactive oxygen species (ROS) and malondialdehyde (MDA). Intracellular biochemical assays demonstrated that HMX induced loss of mitochondrial membrane potential in PC12 cells. Notably, altered expression of brain-derived neurotrophic factor (BDNF) and ionotropic glutamate receptors (iGluRs), as well as an abnormal transcription profile, were also observed in PC12 cells treated by HMX. These findings suggest that HMX exerts toxic effects on PC12 cells, involved in oxidative stress, and disturbances in Ca2+ and BDNF, accompanied by aberrant iGluRs. Overall, the present study helps us better understand the health hazards associated with HMX and provides valuable insights for developing the health protection standards related to HMX exposure.