TBHQ-Overview of Multiple Mechanisms against Oxidative Stress for Attenuating Methamphetamine-Induced Neurotoxicity.

Yuan-Ling Zhao,Yun Wang,Ming Liu,Wei Zhao,Lian Liu,Lillian Barros

doi:10.1155/2020/8874304

Abstract

Methamphetamine is a derivative of amphetamines, a highly addictive central stimulant with multiple systemic toxicity including the brain, heart, liver, lung, and spleen. It has adverse effects such as apoptosis and breakdown of the blood-brain barrier. Methamphetamine is a fatal and toxic chemical substance, and its lethal mechanism has been widely studied in recent years. The possible mechanism is that methamphetamine can cause cardiotoxicity and neurotoxicity mainly by inducing oxidative stress so as to generate heat, eliminate people's hunger and thirst, and maintain a state of excitement so that people can continue to exercise. According to many research, there is no doubt that methamphetamine triggers neurotoxicity by inducing reactive oxygen species (ROS) production and redox imbalance. This review summarized the mechanisms of methamphetamine-induced neurotoxicity including apoptosis and blood-brain barrier breakdown through oxidative stress and analyzed several possible antioxidative mechanisms of tert-butylhydroquinone (TBHQ) which is a kind of food additive with antioxidative effects. As a nuclear factor E2-related factor 2 (Nrf2) agonist, TBHQ may inhibit neurotoxicity caused by oxidative stress through the following three mechanisms: the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, the astrocytes activation, and the glutathione pathway. The mechanism about methamphetamine's toxic effects and its antioxidative therapeutic drugs would become a research hotspot in this field and has very important research significance.

Highlights

According to data from 2018, the global seizures of methamphetamine reached 228 tons and increased by 23% compared with the previous years
TBHQ increases the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) and at the same time enhances the expression of antioxidative genes downstream of Nrf2, moderately activates astrocytes, and reduces the production of inflammatory cytokines, thereby reducing apoptosis and neuronal death [89]
Methamphetamine addiction and chronic poisoning have been widely concerned by society

Summary

Introduction

According to data from 2018, the global seizures of methamphetamine reached 228 tons and increased by 23% compared with the previous years. Toxic doses of methamphetamine can cause hyperthermia, and high core temperature can cause a large amount of dopamine loss in the brain. The study found that under high temperature, the concentration of antisuperoxide anion free radicals and the activity of superoxide dismutase (SOD) were significantly reduced, proving that hyperthermia caused oxidative stress [9]. The scholar’s research showed that abuse of methamphetamine enhanced the level of oxidative stress and lipid peroxidation in the body. The neurotoxicity of methamphetamine is mainly produced by inducing oxidative stress, so antioxidation is of great significance in the prevention and treatment of methamphetamine toxicity. This review briefly explains the neurotoxicity of methamphetamine from apoptosis and blood-brain barrier breakdown, and summarizes the possible antioxidative mechanism of TBHQ from three perspectives. There are only a few related literatures about the effects of TBHQ on methamphetamine, and this review is expected to open up new ideas for the prevention and treatment of methamphetamine neurotoxicity

Methamphetamine and Neurotoxicity

TBHQ and Antioxidative Stress

Findings

Concluding Remarks