Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats

Abstract

Hyperhomocysteinemia has been related to various diseases, including homocystinuria, neurodegenerative and hepatic diseases. In the present study we initially investigated the effect of chronic homocysteine administration on some parameters of oxidative stress, named total radical-trapping antioxidant potential, total antioxidant reactivity, catalase activity, chemiluminescence, thiobarbituric acid-reactive substances, and total thiol content in liver of rats. We also performed histological analysis, evaluating steatosis, inflammatory infiltration, fibrosis, and glycogen/glycoprotein content in liver tissue sections from hyperhomocysteinemic rats. Finally, we evaluated the activities of aminotransferases in liver and plasma of hyperhomocysteinemic rats. Wistar rats received daily subcutaneous injection of Hcy from their 6th to their 28th day of life. Twelve hours after the last injection the rats were sacrificed, liver and plasma were collected. Hyperhomocysteinemia decreased antioxidant defenses and total thiol content, and increased lipid peroxidation in liver of rats, characterizing a reliable oxidative stress. Histological analysis indicated the presence of inflammatory infiltrate, fibrosis and reduced content of glycogen/glycoprotein in liver tissue sections from hyperhomocysteinemic rats. Aminotransferases activities were not altered by homocysteine. Our data showed a consistent profile of liver injury elicited by homocysteine, which could contribute to explain, at least in part, the mechanisms involved in human liver diseases associated to hyperhomocysteinemia.

Carnosine Ameliorates Stress-Induced Glucose Metabolism Disorder in Restrained Mice

“…On the other hand, GYS2, GK, and GLUT2 expressions were lowered in restraint stressed mice. In accordance with previous research, glycogen content and glycogen synthase activity were significantly lowered by the stress reaction (37,42). Hyperglycemia could also reduce glycogen synthase (43) and GK activities (44,45).…”

Effects of Acute Administration of D,L-Homocysteine Thiolactone on the Antioxidative Status of Rat Intestine and Liver

“…Similar results reported Matte et al [5]. They showed the occurrence of oxidative stress and notably reduced antioxidant defenses (enzymatic and non-enzymatic) and increased lipid peroxidation, and infl ammatory infi ltration in the liver of Hcy-treated rats.…”

“…Matte et al [5] showed that homocysteine induced oxidative stress in rat liver. Streck et al [6] demonstrated that homocysteine signifi cantly increased thiobarbituric acid-reactive substances (TBARS), but did not change antioxidant enzymes.…”

Degenerative Liver Disease in Young Beagles with Hereditary Cobalamin Malabsorption Because of a Mutation in the Cubilin Gene

“…Homocysteine has been suggested to cause hepatic damage in mice by oxidative stress, endoplasmatic reticulum stress, and activation of proinflammatory factors 17, 18. Furthermore, hyperhomocysteinemia promotes hepatic inflammation and fibrosis in rats 19. Stellate cells produce collagen types I, III, and IV, which are deposited as a delicate reticulin network in the space of Disse during chronic hepatic injury 20.…”