{"title":"关于 CUMYL-4CN-BINACA 对 Sprague Dawley 大鼠可能产生的神经毒性作用的研究","authors":"Ayşe Lafzi , Tuba Demirci , Neslihan Yüce , Ebru Annaç , Mustafa Çiçek , Turgay Şişman","doi":"10.1016/j.legalmed.2023.102389","DOIUrl":null,"url":null,"abstract":"<div><p>Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood–brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.</p></div>","PeriodicalId":49913,"journal":{"name":"Legal Medicine","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats\",\"authors\":\"Ayşe Lafzi , Tuba Demirci , Neslihan Yüce , Ebru Annaç , Mustafa Çiçek , Turgay Şişman\",\"doi\":\"10.1016/j.legalmed.2023.102389\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood–brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.</p></div>\",\"PeriodicalId\":49913,\"journal\":{\"name\":\"Legal Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2023-12-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Legal Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1344622323001992\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, LEGAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Legal Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1344622323001992","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, LEGAL","Score":null,"Total":0}
A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats
Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood–brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.
期刊介绍:
Legal Medicine provides an international forum for the publication of original articles, reviews and correspondence on subjects that cover practical and theoretical areas of interest relating to the wide range of legal medicine.
Subjects covered include forensic pathology, toxicology, odontology, anthropology, criminalistics, immunochemistry, hemogenetics and forensic aspects of biological science with emphasis on DNA analysis and molecular biology. Submissions dealing with medicolegal problems such as malpractice, insurance, child abuse or ethics in medical practice are also acceptable.