PloS one, 2011-10, Vol.6 (10), p.e25943
2011
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- Autor(en) / Beteiligte
- Titel
- Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats
- Ist Teil von
- PloS one, 2011-10, Vol.6 (10), p.e25943
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hydrogen sulfide (H(2)S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2)S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2)S in carbon tetrachloride (CCl(4))-induced hepatotoxicity, cirrhosis and portal hypertension. Sodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Exogenous H(2)S attenuates CCl(4)-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2)S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0025943Titel-ID: cdi_plos_journals_1965493951
- Format
- –
- Schlagworte
- Actin, Alanine, Alanine transaminase, Alanine Transaminase - blood, Albumin, Animals, Aspartate, Aspartate aminotransferase, Aspartate Aminotransferases - blood, Attenuation, Bile, Biology, Blood Pressure - drug effects, Carbon Tetrachloride, CCL4 protein, Cell adhesion, Cirrhosis, Cystathionine gamma-Lyase - metabolism, Cytochrome, Cytochrome P-450, Cytochrome P-450 CYP2E1 - metabolism, Cytochrome P450, Drinking water, Enzyme inhibitors, Fibroblasts, Fibrosis, Glutathione - metabolism, Heart attacks, Hepatotoxicity, Histology, Hospitals, Hyaluronic acid, Hydrogen, Hydrogen sulfide, Hydrogen Sulfide - blood, Hydrogen Sulfide - pharmacology, Hydrogen Sulfide - therapeutic use, Hydroxyproline, Hydroxyproline - metabolism, Hypertension, Hypertension, Portal - blood, Hypertension, Portal - complications, Hypertension, Portal - drug therapy, Hypertension, Portal - physiopathology, Hypoxia, Inflammation, Inflammation - blood, Inflammation - complications, Inflammation - pathology, Intercellular adhesion molecule 1, Interleukin 6, Interleukins, Ischemia, Lipids, Liver, Liver - drug effects, Liver - enzymology, Liver - pathology, Liver - physiopathology, Liver cirrhosis, Liver Cirrhosis - blood, Liver Cirrhosis - complications, Liver Cirrhosis - drug therapy, Liver Cirrhosis - physiopathology, Liver diseases, Liver Function Tests, Male, Malondialdehyde - metabolism, Medicine, Muscle proteins, Organ Size - drug effects, Oxidation, Oxidative stress, Pathology, Physiology, Portal hypertension, Proteins, Pulmonary hypertension, Rats, Rats, Wistar, Rodents, Serum levels, Smooth muscle, Sodium, Sulfide, Surgery, Toxicity Tests, Acute, Tumor necrosis factor, Tumor necrosis factor-TNF