heroin and Chemical-and-Drug-Induced-Liver-Injury

Researches on heroin are more about addiction and some infectious diseases it causes, but liver fibrosis caused by heroin abuse and the mechanism of heroin hepatotoxicity in addicts are ignored. To explore the mechanism of heroin hepatotoxicity, mice in heroin group were intraperitoneally injected by heroin (10 mg/kg) once a day for 14 consecutive days, while mice in heroin withdraw group underwent another 7 days without heroin administration after the same treatment as heroin group. The levels of alanine aminotransferase （ALT）and aspartate aminotransferase （AST） in serum, as biochemical indexes, were applied to evaluate liver damage. H & E staining and oil red O staining were used to observe the pathological changes of liver. Transcriptomics and metabolomics were applied to detect genes and metabolites in livers. The results of biochemical analysis and pathological examination showed that heroin induced liver damage and lipid loss in mice, and these mice did not return to normal completely after a short-term withdrawal. A total of 511 differential genes and 78 differential metabolites were identified by transcriptomics and metabolomics. These differential genes and metabolites were significantly enriched in pathways like lipid metabolism, arachidonic acid metabolism, glutathione metabolism, TCA cycle. And after undergoing 7-day withdrawal of heroin, most of the above differential genes and metabolites did not return to normal. Our study revealed the hepatotoxicity of heroin and that short-term withdrawal of heroin did not fully restore liver function. In addition, transcriptomics and metabolomics revealed that lipid metabolism and arachidonic acid metabolism may be potential therapeutic targets of heroin hepatotoxicity, providing a basis for the treatment of heroin addiction patients in the future.

Topics: Animals; Arachidonic Acid; Chemical and Drug Induced Liver Injury; Heroin; Liver; Metabolomics; Mice; Transcriptome

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.

Topics: Animals; Animals, Outbred Strains; Biomarkers; Chemical and Drug Induced Liver Injury; Heroin; Heroin Dependence; Liver; Male; Metabolomics; Mice; Phenotype

Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates.

Topics: Adult; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Female; Half-Life; Heroin; Humans; Male; Methadone; Substance-Related Disorders

Topics: Adult; Chemical and Drug Induced Liver Injury; Heroin; Heroin Dependence; Humans; Liver; Male

Topics: Adult; Autoantibodies; Bacterial Infections; Biopsy; Chemical and Drug Induced Liver Injury; Cholestasis, Extrahepatic; Cholestasis, Intrahepatic; Diagnosis, Differential; Female; Halothane; Hepatitis; Hepatitis B Antibodies; Hepatitis B Surface Antigens; Hepatitis, Viral, Human; Heroin; Heroin Dependence; Humans; Hypergammaglobulinemia; Liver; Liver Diseases; Liver Function Tests; Male; Middle Aged

Immediate attention must be given to the respiratory system of the heroin abuser; then he should be given naloxone HCl. Search for evidence of use of additional drugs, which may compound problems. Pulmonary edema, aspiration pneumonia and pulmonary embolization are the most common complications. Infections, particularly endocarditis, and cardiac arrhythmia also occur with heroin overdose. Hepatitis is common. Treatment must include not only attention to the presenting symptoms but also referral to a rehabilitation center when possible.

Topics: Arrhythmias, Cardiac; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Emergency Service, Hospital; Endocarditis; Female; Genital Diseases, Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infections; Male; Methadone; Naloxone; Pulmonary Edema; Respiratory Insufficiency

Liver function tests were performed in 500 young servicemen with a history of drug abuse. Serum glutamic oxaloacetic transaminase (SGOT) level was abnormal in 66% of 68 patients with a history of parenteral drug abuse. Forty-one percent of 432 patients with a history of only nonparenteral drug abuse also had elevated SGOT levels. A high incidence of liver disease in parenteral drug abusers is well established; however, to our knowledge, the magnitude of the problem in nonparenteral drug abusers has not been noted previously. Liver biopsy specimens in 34 of our patients showed either a classic viral hepatitis or a mild nonspecific hepatitis. Limited follow-up suggested a slowly resolving process. We conclude that hepatitis may be a common sequel to epidemic nonparenteral drug abuse.

Topics: Adolescent; Adult; Alkaline Phosphatase; Asia, Southeastern; Aspartate Aminotransferases; Cannabis; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Confidentiality; Hepatitis B Antigens; Heroin; Humans; Liver; Liver Diseases; Liver Function Tests; Male; Military Medicine; Phytotherapy; Substance-Related Disorders; United States

Topics: Acute Kidney Injury; Arrhythmias, Cardiac; Chemical and Drug Induced Liver Injury; Electrocardiography; Female; Fetal Diseases; Fetus; Heart Diseases; Hepatitis A; Heroin; Heroin Dependence; Humans; Hypertension, Pulmonary; Injections, Intramuscular; Injections, Intravenous; Injections, Subcutaneous; Lung Diseases; Male; Maternal-Fetal Exchange; Methods; Neurologic Manifestations; Pneumonia, Aspiration; Pregnancy; Pulmonary Edema; Pulmonary Embolism; Respiratory Insufficiency; Skin Diseases

Topics: Abscess; Aneurysm, Infected; Arteritis; Arthritis; Chemical and Drug Induced Liver Injury; Drainage; Endocarditis; Gastrointestinal Diseases; Hand; Heart Valve Prosthesis; Heroin; Heroin Dependence; Humans; Injections, Intra-Arterial; Injections, Intravenous; Injections, Subcutaneous; Lung Diseases; Myositis; Narcotics; Pancreatitis; Phlebitis; Substance-Related Disorders; Surgical Procedures, Operative

Topics: Administration, Intranasal; Adolescent; Adult; Alanine Transaminase; Cannabis; Chemical and Drug Induced Liver Injury; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Liver; Male; Military Medicine; Smoking; United States; Vietnam

Topics: Abscess; Adolescent; Adult; Chemical and Drug Induced Liver Injury; Chromosomes; Endocarditis; Female; Heroin; Heroin Dependence; Humans; Liver; Lung Diseases; Male; Methadone; Nephrotic Syndrome; Nervous System Diseases; Osteomyelitis

Topics: Alcoholism; Chemical and Drug Induced Liver Injury; Hepatitis A; Hepatitis B; Heroin; Heroin Dependence; Humans; Liver Diseases; Substance-Related Disorders

Topics: Adolescent; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Cholesterol; Drug Contamination; Hepatitis B Antigens; Heroin; Humans; Hypnotics and Sedatives; Liver Function Tests; Needles; Substance-Related Disorders

Topics: Acute Disease; Adolescent; Adult; Autopsy; Chemical and Drug Induced Liver Injury; Female; Hepatitis A; Hepatitis B; Heroin; Humans; Liver; Liver Diseases; Lymph Nodes; Male; Morphine Dependence; Necrosis; Pulmonary Edema

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs. Sydney E. Salmon and Robert W. Schrier, Assistant Professors of Medicine, under the direction of Dr. Lloyd H. Smith, Jr., Professor of Medicine and Chairman of the Department of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, San Francisco, Ca. 94122.

Topics: Bacterial Infections; Chemical and Drug Induced Liver Injury; Endocarditis, Bacterial; Heroin; Humans; Lung Diseases; Malaria; Substance Withdrawal Syndrome; Substance-Related Disorders; Tetanus

Topics: Acute Disease; Adolescent; Adult; Chemical and Drug Induced Liver Injury; Duodenal Ulcer; Female; Heart Failure; Heroin; Humans; Jaundice; Male; Maryland; Middle Aged; Neurotic Disorders; Pneumonia; Pulmonary Edema; Pulmonary Fibrosis; Radiography; Sarcoidosis; Substance-Related Disorders; Tetanus

Topics: Adolescent; Biliary Tract Diseases; Brain Diseases; Chemical and Drug Induced Liver Injury; Child; Chronic Disease; Electroencephalography; Exchange Transfusion, Whole Blood; Female; Hepatic Encephalopathy; Hepatitis; Heroin; Humans; Male; Methods; Neurologic Manifestations; Plasma Substitutes; Plasmapheresis