Cardiac and liver organ iron contents, dry-weight iron concentrations, wet-to-dry weight ratio and organ weights are summarized in . Hearts and livers from iron-loaded animals demonstrated 9- to 115-fold higher organ iron content than controls. Iron-loaded livers also exhibited greater total organ weight and lower wet-to-dry weight ratio than livers from control animals. Taurine-treated animals demonstrated greater dry-weight liver iron concentrations (41.9 vs. 35.8 mg/g) but total liver iron content was not different. No other differences were observed in heart and liver iron concentration or content between the three treatment groups.
Cardiac and hepatic organ iron contents, dry-weight iron concentrations, wet-to-dry weight ratio and organ weights
Liver enzymes and serum iron are summarized in . Serum iron was tightly correlated (r2 = 0.92) with wet-weight liver iron concentration (not shown). Serum iron was significantly elevated in all iron-loaded animals, but particularly the taurine group. AST and ALT were correlated with one another (r2 = 0.7) but not with serum or hepatic iron concentration. AST trended higher in the iron-alone and taurine-treated groups but not in the vitamin E/selenium-treated animals. ALT was unchanged across treatment groups.
Liver enzymes and serum iron
depicts cardiac and hepatic iron staining with Prussian blue for each treatment group after 10 weeks of iron loading. Cardiac iron demonstrates intense staining in interstitially distributed endothelial cells and more diffuse myocyte staining as previously described [17
]. In the liver, iron-treated animals showed iron distribution in hepatocytes, Kupffer cells, and large aggregates of phagocytic cells. There was no visible change in iron distribution between the three groups for either liver or heart.
Histological analysis of heart and liver after 10 weeks of iron loading. Groups were stained with Prussian blue iron stain. No fundamental changes in hepatic and cardiac iron distribution were observed between the three groups.
MDA levels of heart and liver are shown in . In the heart, iron loading led to significantly higher MDA levels, reflecting increased oxidative damage. MDA levels in taurine-treated animals were 11% lower compared to the iron-only group, but this difference did not reach statistical significance. There was no beneficial effect of vitamin E/selenium.
Fig. 2 MDA levels in liver (a) and heart (b). a Iron overload in the liver did not cause MDA levels to rise significantly compared to hepatic MDA levels of unloaded gerbils (control). b Cardiac MDA levels were significantly elevated in all three treatment groups (more ...)
No significant differences were detected in liver MDA levels between the iron group () and the control group suggesting that iron overload did not increase MDA production in the liver. As a result, no treatment differences could be observed.
demonstrates liver and heart GPx activity levels. Iron loading without antioxidants reduced GPx activity by 35%. GPx activity was spared in taurine-treated animals (13% less than controls, p = nonsignificant). Vitamin E/selenium produced intermediate results with GPx activity 22% less than controls.
Fig. 3 Measurement of GPx activity levels in liver (a) and heart (b). a Significantly reduced hepatic GPx activity in iron-only and vitamin E/selenium animals was observed in comparison to control. Taurine seemed to have a protective effect on GPx activity. (more ...)
GPx activity in the heart was qualitatively similar but changes did not reach statistical significance. Iron loading produced 18.8% lower GPx activity; this deficit was only 10% with concomitant taurine treatment. Surprisingly, vitamin E/selenium supplementation lowered cardiac GPx activity 37.5% with respect to control, indicating a detrimental effect of this therapy in the heart.
Selenium concentrations in the heart and liver are plotted in . Iron loading reduced selenium levels in both organs by 34 and 47%, respectively; however, interanimal variability was sufficiently high that these changes did not reach statistical significance. Only the vitamin E/selenium-supplemented group demonstrated significantly elevated heart selenium levels (127% of control), while no significant differences were noted in the other groups or the liver ().
Fig. 4 Depiction of selenium concentrations in heart (a) and liver (b). Selenium levels were reduced in iron-loaded animals compared to controls, although this was not statistically significant. Significantly elevated levels of selenium were only found in the (more ...)