Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; Guangdong Province Translational Forensic Medicine Engineering Technology Research Center, Sun Yat-sen University, Guangzhou, China.
Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 232 Outer Ring Road, University Town, Guangzhou 510006, China.
Life Sci. 2021 Dec 15;287:120103. doi: 10.1016/j.lfs.2021.120103. Epub 2021 Oct 29.
Heroin is a semi-synthetic opioid that is commonly abused drugs in the world. It can cause hepatic injury and lead to multiple organs dysfunction to its addicts. Only a few reports exist on the metabolic changes and mechanisms in the liver of heroin-addicted mice with hepatic injury.
Twelve adult male Kunming mice (30-40 g) were divided into two groups randomly. The mice in the heroin-addicted group were injected subcutaneously in the first ten days with an increased dosage of heroin from 10 mg/kg to 55 mg/kg. The dosage was then stabilized at 55 mg/kg for three days. The control group was injected with the same amount of saline in the same manner. The hepatic injury was confirmed through the combination of histopathological observation and aminotransferase (AST) and alanine aminotransferase (ALT) determination. The withdrawal symptoms were recorded and used for assessment of heroin addiction. Eventually, liver metabolic biomarkers of heroin-addicted mice with hepatotoxicity were measured using UHPLC-MS/MS.
Biochemical analysis and histopathological observation showed that heroin-addicted mice had a liver injury. The liver metabolites of heroin-addicted mice changed significantly. Metabonomics analysis revealed 41 metabolites in the liver of addicted heroin mice as biomarkers involving 34 metabolic pathways. Among them, glutathione metabolism, taurine and hypotaurine metabolism, vitamin B2 metabolism, riboflavin metabolism, and single-carbon metabolism pathways were markedly dispruted.
Heroin damages the liver and disrupts the liver's metabolic pathways. Glutathione, taurine, riboflavin, 4-pyridoxate, folic acid, and methionine are important metabolic biomarkers, which may be key targets of heroin-induced liver damage. Thus, this study provides an in-depth understanding of the mechanisms of heroin-induced hepatotoxicity and potential biomarkers of liver damage.
海洛因是一种半合成阿片类药物，是世界范围内常见的滥用药物。它可以导致肝损伤，并导致其成瘾者多个器官功能障碍。只有少数报道存在于海洛因成瘾小鼠肝损伤的肝脏代谢变化和机制。
将 12 只成年雄性昆明小鼠（30-40g）随机分为两组。海洛因成瘾组在前 10 天内通过皮下注射逐渐增加剂量从 10mg/kg 增加到 55mg/kg，然后剂量稳定在 55mg/kg 3 天。对照组以相同的方式注射等量的生理盐水。通过组织病理学观察和转氨酶（AST）和丙氨酸氨基转移酶（ALT）测定相结合来确认肝损伤。记录戒断症状并用于评估海洛因成瘾。最终，使用 UHPLC-MS/MS 测量具有肝毒性的海洛因成瘾小鼠的肝脏代谢生物标志物。
生化分析和组织病理学观察表明，海洛因成瘾小鼠有肝损伤。海洛因成瘾小鼠的肝脏代谢物发生了显著变化。代谢组学分析显示，成瘾海洛因小鼠肝脏中有 41 种代谢物作为生物标志物涉及 34 种代谢途径。其中，谷胱甘肽代谢、牛磺酸和次牛磺酸代谢、维生素 B2 代谢、核黄素代谢和一碳代谢途径明显失调。
海洛因损害肝脏并破坏肝脏的代谢途径。谷胱甘肽、牛磺酸、核黄素、4-吡哆酸、叶酸和蛋氨酸是重要的代谢生物标志物，可能是海洛因引起肝损伤的关键靶点。因此，本研究深入了解了海洛因引起肝毒性的机制和潜在的肝损伤生物标志物。
