Methcathinone Induces Oxidative Stress to Mediate Neurotoxicity Through Activating Apoptosis and Autophagy
27 Pages Posted: 16 Jan 2019More...
Background: Methcathinone (CAT) acts as a designer psychostimulant and the beta-keto analog of methamphetamine, is globally abused and cause serious neurological conditions. The aim of this study is to analyze neurotoxicity of Methcathinone (CAT) to verify the hypothesis of unbalanced oxidative stress and the evaluation of apoptotic response and autophagy by sub-acute exposure to high dosage injection.
Methods: To address these issues, we measured the body temperature and stereotyped motor activity during rats model setting by CAT injection in 15-day. Biochemical markers of oxidative stress were evaluated, and the activity of anti-oxidative enzymes was found significantly lower in the brains of rats that had different doses of CAT.
Findings: The mechanism of the toxicological effect of CAT is proved to be partly induced by apoptotic pathway according to multiple biochemical and immunohistological methods, as well as expression of nNOS, ratios of LC3-II to LC3-I and cleaved caspase3 to procaspase3. Furthermore, we detected the inhibition of NAC to CAT induced-apoptotic and autophagy pathways effected largely compared to the CAT group through activity of SOD, GSH, GSH-PX, CAT and MDA, TUNEL staining and expression of Atg-7, Beclin-1 and ratio of LC3-II to LC3-I, which decreased neurotoxicity. Our results highlight the central role of oxidative stress in CAT neurotoxicity, as high levels of apoptosis and autophagy can promote the progression of neurotoxicity.
Funding Statement: This study was supported by National Natural Science Foundation of China (Grant No. 81501632).
Declaration of Interests: The authors declare that they have no competing interests.
Ethics Approval Statement: All animal procedures were conducted between 8:00 A.M. and 8:00 P.M. in strict accordance with the “Hubei Administration Rule of Laboratory Animal” and were approved by the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology, Tongji Medical College, China (approval No. Y20100377). The description of animal procedures meets the ARRIVE recommended national standard “Laboratory Animal-Requirements of Environment and Housing Facilities”.
Keywords: methcathinone; oxidative stress; neurotoxicity; apoptosis; autophagy
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