Oxidative stress in portal hypertension-induced rats with particular emphasis on nitric oxide and trace metals

To investigate the oxidative-stress-related changes in rats with portal hypertension with particular emphasis on nitric oxide (NO) and trace metals.

Cirrhosis was induced by partial portal vein ligation (PVL) in Wistar rats. The lipid peroxidation marker (malondialdehyde, MDA), antioxidant defense enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and agents known to have antioxidant features including nitric oxide (NO), zinc (Zn), copper (Cu) were determined both in serum and in liver tissue at 4 wk after surgery in PVL and sham-operated rats. Portal pressure of all experimental animals was measured. MDA was detected by thiobarbituric acid reactivity assay. SOD activity was determined by inhibition of nitroblue tetrazolium reduction with xanthine/xanthine oxidase used as a superoxide generator. CAT activity was determined by the breakdown of hydrogen peroxide. GSH concentrations were measured by using metaphosphoric acid for protein precipitation and 5'-5'-dithio-bis-2-nitrobenzoic acid for color development. NO was detected by the Griess method after reduction of nitrate to nitrite with nitrate reductase, and the concentrations of Zn and Cu were measured by a Shimadzu 680 AA atomic absorption spectrometer. Histopathological confirmation was done under light microscope. Statistical analyses were done by Student's t-test, and significance of the difference was tested by the unpaired Mann-Whitney test. P<0.05 was considered statistically significant.

Histopathological studies confirmed PVL-induced cirrhotic changes. There was a statistically significant difference in portal pressure between PVL and control groups (P<0.001). The results showed significant increases in the levels of MDA and NO in both tissue and serum (P<0.05 and P<0.001, respectively in tissue; P<0.001 for each in serum), and Zn only in tissue (P<0.001) in rats with PVL compared with sham-operated rats. Besides, PVL rats exhibited reduced plasma and tissue GSH, CAT, SOD (P<0.001 for each). Serum and tissue Cu concentration did not change.

Our findings suggest that PVL in rats induces important biochemical and molecular changes related to oxidative stress in the liver.