A recent study found that rats with advanced fibrosis that were administered a short-term dose of losartan-M6PHSA had reduced liver inflammation and fibrosis. Those animals treated with oral losartan alone did not experience a similar reduction in disease activity. Results of this study appear in the March issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.
Liver fibrosis a consequence of liver disease was thought to be irreversible and only transplantation of the liver would offer survival to the patient. Doctors now believe that early detection of fibrosis offers potential for therapies that prevent further liver scarring and the imminent need for transplantation.
In the current study, a Spanish research team led Ramón Bataller, M.D., from the Hospital Clínic in Barcelona investigated such a treatment, losartan-M6PHSA, in rat models. Losartan is an angiotensin (AT1) receptor blocker that was linked to mannose-6-phosphate modified human serum albumin (M6PHSA), a selective drug carrier targeting hepatic stellate cells (HSC). An average of 7 losartan molecules were coupled to M6PHSA. The study verified that losartan-M6PHSA accumulates in the fibrotic liver only, and other organs such as the lungs, heart, spleen and kidneys did not display the conjugate.
Researchers induced liver fibrosis in male rats by bile duct ligation to study short-term treatment outcomes. In both models, rats were given daily injections of saline, losartan-M6PHSA (3.3 mg/kg/day, to 125 µg losartan/kg), M6PHSA alone (3.3 mg/kg/day), or oral losartan (5 mg/kg/day). Bile duct-ligated rates treated with saline of M6PHSA alone showed severe fibrosis. "Animals treated with losartan-M6PHSA displayed less collagen deposition with less frequent formation of bridging fibrosis," said Dr. Bataller. "Short-term oral treatment with losartan alone did not reduce fibrosis or the amount of collagen."
In the long-term results, advanced liver fibrosis was established in male rats by chronic treatment of carbon tetrachloride (CCl4 ). Treatment by saline, losartan-M6PHSA or M6PHSA alone was administered twice a week for three weeks. "While losartan-M6PHSA was able to reduce collagen synthesis, the degree of fibrosis reduction was not significant. Further studies identifying the ideal route and drug dosage for long-term treatment are clearly required," concluded Dr. Bataller.
Article: "Reduction of Advanced Liver Fibrosis by Short-term Targeted Delivery of an Angiotensin Receptor Blocker to Hepatic Stellate Cells in Rats." Montserrat Moreno, Teresa Gonzalo, Robbert J. Kok, Pau Sancho-Bru, Marike van Beuge, Josine Swart, Jai Prakash, Kai Temming, Constantino Fondevila, Leonie Beljaars, Marie Lacombe, Paul Vd Hoeven, Vicente Arroyo, Klaas Poelstra, David A. Brenner, Pere Ginès and Ramón Bataller. Hepatology; Published Online: March 1, 2010 (DOI: 10.1002/hep.23419); Print Issue Date: March 2010.
Media wishing to receive a PDF of the article may contact firstname.lastname@example.org
Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://www3.interscience.wiley.com/journal/106570044/home.
Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or www.interscience.wiley.com.
Dawn Peters | EurekAlert!
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy