Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats

Chronic liver injury and cirrhosis leads to liver failure. Hyperammonemia is a deleterious consequence of liver failure. On the other hand, oxidative stress seems to play a pivotal role in the pathogenesis of liver fibrosis as well as in the cytotoxic mechanism of ammonia. There is no promising therapeutic agent against ammonia-induced complications. The present study was conducted to evaluate the role of carnosine (CA) administration on liver pathological changes, elevated plasma ammonia, and its consequent events in cirrhotic rats.

Bile duct ligated (BDL) rats were used as a model of cirrhosis. CA (250, 500, and 1000mg/kg, daily, i.p) was administered for 28 consecutive days to BDL animals. At the end of treatments, markers of oxidative stress and liver fibrosis was determined in liver and serum biomarkers of liver injury and plasma ammonia was assessed. Moreover, changes in animals' locomotor activity were monitored.

Severe bridging fibrosis, inflammation, and necrosis in liver, along with elevated serum biomarkers of liver injury were evident in BDL animals. Furthermore, plasma ammonia was drastically elevated in cirrhotic rats and animals' locomotor activity was suppressed. It was found that CA (250, 500, and 1000mg/kg, daily, i.p) significantly alleviated liver injury and its consequent events in cirrhotic rats. The data suggested that CA is not only a useful and safe agent to preserve liver function, but also prevented hyperammonemia and brain damage as a deleterious consequence of cirrhosis and liver failure.