hypericum and Chemical-and-Drug-Induced-Liver-Injury

BACKGROUND This network pharmacology study aimed to identify the active compounds and molecular mechanisms involved in the effects of Hypericum japonicum on cholestatic hepatitis. We validated the findings in an alpha-naphthylisothiocyanate (ANIT) rat model of hepatotoxicity. MATERIAL AND METHODS The chemical constituents and targets of H. japonicum and target genes previously associated with cholestatic hepatitis were retrieved from public databases. A network was constructed using Cytoscape 3.7.2 software and the STRING database and potential protein functions were analyzed based on the public platform of bioinformatics. ANIT was used to induce cholestatic hepatitis in a rat model using 36 Sprague-Dawley rats, and this model was used to investigate intervention with 3 doses of quercetin (low-dose, 50 mg/kg; medium-dose, 100 mg/kg; and high-dose, 200 mg/kg), the main active component of H. japonicum. Levels of serum biochemical indexes were measured by commercial kits, and the messenger RNA (mRNA) levels of markers of liver and mitochondrial function and oxidative stress were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS The main active ingredients of H. japonicum were quercetin, kaempferol, and tetramethoxyluteolin, and their key targets included prostaglandin G/H synthase 2 (PTGS2), B-cell lymphoma-2 (BCL2), cholesterol 7-alpha hydroxylase (CYP7A1), and farnesoid X receptor (FXR). Quercetin intervention promoted recovery from cholestatic hepatitis. CONCLUSIONS The findings from this research provide support for future research on the roles of quercetin, kaempferol, and tetramethoxyluteolin in human liver disease and the roles of the PTGS2, BCL2, CYP7A1, and FXR genes in cholestatic hepatitis.

Topics: 1-Naphthylisothiocyanate; Animals; Chemical and Drug Induced Liver Injury; Cholangitis; Cholestasis; Disease Models, Animal; Hepatitis; Hepatocytes; Hypericum; Kaempferols; Liver; Liver Diseases; Luteolin; Male; Oxidative Stress; Plant Extracts; Quercetin; Rats; Rats, Sprague-Dawley

This study is aimed to investigate the effects of Camellia sinensis (CS), Hypericum perforatum (HP) and Urtica dioica (UD) in kidney and liver injury induced by carbon tetrachloride (CCl4) in rats. Highly toxic CCl4 which is used as a solvent in industry comprises experimental toxicity in rats and is widely used in hepatotoxicity and other tissue injury models. The purpose of this investigation is to monitor blood and various tissues by biochemical and histopathological analysis for preventive effects of CS, HP and UD on oxidative stress induced by administration of CCl4 and to enlighten the probable mechanism. Fifty eight rats were divided into five groups; sham group (Group 1, untreated animals), control CCl4 treated group (Group 2), HP extract-treated group (Group 3), UD extract-treated group (Group 4), CS extract-treated group (Group 5). All rats were anaesthetized at the end of the experiment and the blood was collected from each rat. Afterwards, tissue specimens were obtained. The tissue specimens were immersed in 10% formaldehyde for 24 hours. After routine tissue processing, the liver, kidney and stomach were sectioned in 5µm thickness, stained in hematoxylin and eosin. The histological study was performed by using light microscope. The serum marker enzymes were found to be significantly increased in CCl4-induced liver and kidney damage when compared with the sham group (p<0.05). However, treatment with CS, HP, and UD extracts resulted in decreased activity of serum enzymes. Malondialdehyde (MDA) levels were decreased by 20.51±0.95, 27.98±1.58, and 32.39±3.1 nmol/g wet weight protein in kidney homogenates and 16.65±1.75, 17.22±0.71 and 18.92±71 nmol/g wet weight protein in liver homogenates in CS, HP and UD treated groups, respectively. Our results have shown that additive antioxidants like CS, HP and UD will aid in diminishing these deviations in cases of liver and kidney dysfunction.

Topics: Acute Kidney Injury; Animals; Antioxidants; Camellia sinensis; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Hypericum; Malondialdehyde; Oxidative Stress; Phytotherapy; Plant Extracts; Protective Agents; Rats; Rats, Wistar; Superoxide Dismutase; Urtica dioica

A patient is admitted with complaints of recent onset nausea, discomfort, jaundice and blood tests that reveal severe hepatitis. At the time, she had been taking medication with

Topics: Adult; Aminopyridines; Analgesics; Chemical and Drug Induced Liver Injury; Diagnosis, Differential; Drug Interactions; Fatal Outcome; Female; Hepatic Encephalopathy; Humans; Hypericum; Liver Failure, Acute; Shock, Septic

Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)-induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced lethality. Paracetamol-induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL-1β, TNF-α, and IFN-γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS˙(+) ) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol-induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol-induced cytokine production, neutrophil recruitment, and oxidative stress.

Topics: Acetaminophen; Alanine Transaminase; Animals; Anthracenes; Anti-Inflammatory Agents; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Glutathione; Hypericum; Inflammation; Male; Mice; Oxidative Stress; Perylene; Phloroglucinol; Plant Extracts; Plants, Medicinal; Quercetin; Rutin; Terpenes; Tumor Necrosis Factor-alpha

We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure.

Topics: Aged; Chemical and Drug Induced Liver Injury; Fabaceae; Female; Humans; Hypericum; Phytotherapy; Plant Extracts

Topics: Adult; Chemical and Drug Induced Liver Injury; Female; Humans; Hypericum; Phytotherapy

In an otherwise healthy 48-year-old female patient, acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to 752 U/l), inconspicuous hepatitis serology findings, negative autoantibody status and negative virus serology was observed after a 10-week long intake of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day). Biopsy of the liver showed lobular and portal necroinflammatory activity without indication of cirrhosis.. Due to these findings with proven T-cell activity (lymphocyte typing, neopterin determination) as well as the aetiopathology, this form of hepatitis with histological characteristics of a nutritive/medicinal toxic origin was classified as induced immunologic idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune hepatitis.. Discontinuation of the existing medication and simultaneous onset of immunosuppressive combination therapy of cortisone, azathioprine and ursodeoxycholic acid resulted in normalisation of the liver parameters within a period of two months.. On the one hand, it appears that simultaneous intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On the other hand, an immune-mediated mechanism, induced by kava-kava, cannot be completely excluded in the present case. It must be stressed that in patients with autoimmune hepatitis, precise history of medication intake should also be available.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Biopsy; Chemical and Drug Induced Liver Injury; Drug Synergism; Female; Hepatitis, Autoimmune; Humans; Hypericum; Immunosuppressive Agents; Kava; Liver; Middle Aged; Plant Preparations

Topics: Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Hepatitis, Autoimmune; Humans; Hypericum; Kava; Phytotherapy; Plant Extracts; Transaminases

Topics: Animals; Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Humans; Hypericum; Kava; Plant Preparations

Topics: Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Humans; Hypericum; Kava; Phytotherapy; Plant Preparations

Topics: Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Humans; Hypericum; Kava; Plant Preparations; Pyrones

Hypericum androsaemum L. (Guttiferae) is a medicinal plant with antioxidant activity. Increasing evidence regarding free radical generating agents suggests that hepatotoxic-related disorders may involve reactive oxygen species (ROS). The purpose of this study was to investigate the protective effect of Hypericum androsaemum infusion on isolated rat hepatocytes oxidative injury induced by tert-butyl hydroperoxide (t-BHP). The results showed that pretreatment of the cells with this infusion (16, 62 and 250 microg/ml) prevented the leakage of lactate dehydrogenase (LDH) and lipid peroxidation caused by a 30-min treatment with t-BHP (1mM). However, infusion-induced alterations on glutathione homeostasis were noticed, as it was observed by the increase in glutathione oxidised form (GSSG) and depletion in total glutathione levels, which indicates that plant-derived antioxidant extracts may not be considered a generalised way of treating pro-oxidant-related diseases.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Hepatocytes; Hypericum; Lipid Peroxidation; Liver; Male; Phytotherapy; Plant Extracts; Plant Leaves; Protective Agents; Rats; Rats, Wistar; tert-Butylhydroperoxide