Intestinal and Cardiac Damage during Liver Cirrhosis Role of Nitric Oxide

Abstract

Rats were treated with intraperitoneal injection of TAA (200mg/Kg body weight) in saline twice a week for six months. The animals were sacrificed at monthly intervals from 1 month to 6 months after TAA administration to evaluate changes in the liver, intestine and heart during development of liver cirrhosis, Cirrhosis was established in rats by histology after 3 months of TAA treatment. In liver, an increase in nitrate levels both in the homogenate and mitochondria were demonstrated suggesting the role of nitric oxide (NO) in development of cirrhosis. This increase in nitrate levels was accompanied by decreased arginase activity in the homogenate, especially at later stages after cirrhosis development and increased arginase activity in mitochondria. The decreased arginase activity in the liver resulted in decreased citrulline levels. Intestinal alterations were evident during liver cirrhosis in the intestine as evaluated by histology. During liver cirrhosis, nitrate levels in the intestine were increased both in the homogenate and mitochondria. The increase in nitrate was accompanied by decreased arginase in the homogenate and mitochondria suggesting that arginase can modulate NO production in the intestine. The increase in NO in the intestine during liver cirrhosis is accompanied by posttranslational modification of a number of intestinal proteins as well as inhibition of mitochondrial complex I and IV activity. In addition to these changes in the intestine, cardiac alterations were also evident in liver cirrhosis by ultrastructural studies. During liver cirrhosis oxidative stress was evident in the heart homogenate and mitochondria as evidenced by increased markers of oxidative stress such as malondialdehyde, conjugated diene, protein carbonyl and decrease in total thiols. This elevation in oxidative stress was accompanied by altered cardiac mitochondrial functional parameters such as respiratory control ratio, MTT reduction and mitochondrial swelling. newline