Biochemical and morphologic effects after extended liver resection in rats: preliminary results.

After hepatic resection and transplantation with a partial graft, death and regeneration of the hepatocytes coexist in the liver. However, when the functional liver mass is inadequate to ensure a proper balance between regeneration vs functional and metabolic demands, small-for-size syndrome develops. We assessed the early effects of extended hepatic resection on liver function in a rat model. Six male Sprague-Dawley rats underwent 80% resection of the liver, and 6 rats served as a control group. At 6 hours after resection, blood samples were obtained from the hepatic vein for measurement of reduced glutathione (GSH), oxidized glutathione (GSSG), and hepatic venous oxygen saturation (Shvo(2)), and for standard liver function tests including determination of concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, and total bilirubin. The remnant lobe was removed for GSH assay and histopathologic analysis. In the resection group, values were significantly higher for ALT (P = .002), AST (P = .002), and Shvo(2) (P = .01), whereas a significant decrease was observed for blood GSH (P = .009) but not liver GSH. Also in the resection group, we observed characteristic hepatocyte vacuolization with a gradient from periportal acinar zone 1 to the centrolobular area, the presence of hemorrhagic necrosis, and several leukocyte adhesions. The Shvo(2) and GSH data suggest early alteration of oxygen metabolism, as demonstrated by the reduction in oxygen uptake and decreased liver GSH secretion, with preservation of hepatic GSH. Mitochondrial dysfunction and oxidative injury seem to have a crucial role in early onset of liver damage.

Whey proteins influence hepatic glutathione after CCl4 intoxication.

Whey proteins (WP) are known to contain more cysteine than casein (CAS), so it is suggested that they should ameliorate the oxidative equilibrium in the organisms. To evaluate the influence of a WP-based diet on liver glutathione (GSH) content, male Sprague-Dawley rats were fed for 3 weeks a balanced liquid diet containing either WP or CAS as main source of protein. Liver GSH content was evaluated at the end of the treatment by high performance liquid chromatography (HPLC), both in basal conditions and after oxidative stress induced by CCl4 acute intoxication. In basal conditions, WP diet significantly increased hepatic GSH in comparison to CAS diet. After CCl4 intoxication, hepatic GSH was negligibly increased in CAS group, while its increase was much more marked in WP group, so that the difference between the two diets was significant; this suggests that WP provided rats with better ability to increase their GSH synthesis in case of need.