The cure for cirrhosis
Increased pressure in the vessels carrying blood to the liver for purification, the so–called portal hypertension, is the most threatening condition in cirrhosis of the liver, which is associated with the most dangerous complications of the disease. A group of researchers from the National Yang-Ming University (National Yang–Ming University, Taiwan) reported the successful use of the drug Aleglitazar in rats, an agonist of alpha and gamma receptors activated by peroxisomal proliferators (PPARa/γ). The drug was developed for the treatment of type 2 diabetes, but in clinical studies caused too many side effects.
In the rat model of cirrhosis, he fought inflammation, vasoconstriction (vasoconstriction), inhibited the formation of new vessels, suppressed the production of tumor necrosis factor (TNF-alpha) in the liver.
Cirrhosis of the liver is the main cause of portal hypertension. Increased resistance in the portal vessels of the liver leads to increased pressure in the veins of the spleen, esophagus, stomach. As a result, splenomegaly develops (pathological enlargement of the spleen), fluid exudation into the abdominal cavity (ascites), varicose veins of the esophagus and other conditions.
In an experiment on rats with cirrhosis of the liver, the administration of aleglitazar for 21 days led to the suppression of fibrogenesis – the replacement of functioning hepatocytes with scar tissue. In addition, the process of formation of new vessels and portosystemic anastomoses was slowed down, through which blood from the portal vein was discharged into other vessels, bypassing filtration in the liver. Aleglitazar restored the previously increased vascular permeability, reduced damage to the intestinal mucosa.
The multiple effect of aleglitazar is due to the tropicity in two types of receptors: it activates PPARy in the liver and PPARa in the intestine. The therapeutic effect is associated with the suppression of inflammation and TNF-alpha.
The authors write that the use of PPARa/γ agonists is a promising direction for the treatment of portal hypertension in cirrhosis of the liver and reducing the severity of complications associated with it.
Article by H. C. Tsai et al. Beneficial Effects of the Peroxisome Proliferator-Activated Receptor α/γ Agonist Aleglitazar on Progressive Hepatic and Splanchnic Abnormalities in Cirrhotic Rats with Portal Hypertension is published in The American Journal of Pathology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Researchers find a promising new approach for treating liver cirrhosis.