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
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
24.05.2017 | Life Sciences
24.05.2017 | Life Sciences
24.05.2017 | Physics and Astronomy