title: The effect of the angiotensin II receptor, type 1 receptor antagonists, losartan and telmisartan, on thioacetamide-induced liver fibrosis in rats.
abstract: It has been reported previously that the density of angiotensin II receptors is increased in the rat liver in experimentally-induced fibrosis. We hypothesized that pharmacological blockade of angiotensin receptors may produce beneficial effects in models of liver fibrosis. In this study, we used the widely used thioacetamide (TAA)-induced model of liver fibrosis (300 mg/L TAA ad libitum for 12 weeks). Rats received daily injections (i.p), lasting 4 weeks of the angiotensin II type 1 receptor antagonists, losartan 30 mg/kg (TAA + L) or telmisartan 10 mg/kg (TAA + T) and were compared to rat that received TAA alone. Chronic treatment with losartan and telmisartan was associated with a significant reduction in the activity of alkaline phosphatase, and decreased concentrations of tumor necrosis factor-alpha and transforming growth factor beta-1 compared to controls. We also found a significant reduction interleukin-6 in rats receiving telmisartan (P < 0.05) but not losartan. Both treatments increased the concentration of liver glutathione along with a concomitant decrease of GSSG compared to controls. In addition, increased paraoxonase 1 activity was observed in the serum of rats receiving telmisartan group compared to the TAA alone controls. Finally, histological evaluation of liver sections revealed losartan and telmisartan treatment was associated with reduced inflammation and liver fibrosis. Taken together, these results indicate that both telmisartan and losartan have anti-inflammatory and anti-oxidative properties in the TAA model of liver fibrosis. These finding add support to a growing body of literature indicating a potentially important role for the angiotensin system in liver fibrosis and indicate angiotensin antagonists may be useful agents for fibrosis treatment.
authors: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors: G
authors: G
authors: Czechowska
authors: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland. celinski.krzysztof@gmail.com.
authors: K
authors: K
authors: Celinski
authors: Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland.
authors: A
authors: A
authors: Korolczuk
authors: Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.
authors: G
authors: G
authors: Wojcicka
authors: Independent Laboratory of Medical Biology, Medical University of Lublin, Lublin, Poland.
authors: J
authors: J
authors: Dudka
authors: Department of Clinical Immunology, Medical University of Lublin, Lublin, Poland.
authors: A
authors: A
authors: Bojarska
authors: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors: A
authors: A
authors: Madro
authors: Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
authors: T
authors: T
authors: Brzozowski
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D043303:Aryldialkylphosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D017208:Rats, Wistar; D000077333:Telmisartan; D013853:Thioacetamide
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D016207:Cytokines; D013853:Thioacetamide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C572204:Pon1 protein, rat; D000469:Alkaline Phosphatase; D043303:Aryldialkylphosphatase; D005978:Glutathione; D019808:Losartan; D000077333:Telmisartan; D019803:Glutathione Disulfide