Abstract
The guinea pig model of iron overload, described in the preceding article, was used to investigate the mechanism of excess iron toxicity in hepatic and cardiac tissues. Effects of iron overload on both lysosomal membrane fragility and membrane peroxidation were studied. The free activity of selected myocardial and hepatic lysosomal enzymes, in addition to serum activity, was measured in guinea pigs treated with iron dextran (0.25, 0.5, 1.0, and 2.0 g Fe/kg body weight); controls received dextran. Levels of malondialdehyde were also determined in whole homogenates of heart and liver in animals loaded with 0.5 and 1.5 g Fe/kg of iron dextran. Results indicated that the free activity of hepatic glucosaminidase (p < 0.05) and β-glucuronidase (p < 0.05) were significantly elevated at all levels of iron loading; hepatic acid phosphatase was increased at all but the lowest iron dose. Similarly, increased serum glucosaminidase activity was observed (p < 0.01) at all dose levels. When compared to pooled controls, the free activity of myocardial glucosaminidase was also elevated (p < 0.05) at all levels of loading. However, myocardial acid phosphatase was increased only at the highest iron dose (p < 0.01). Increased malondialdehyde was measured at the high iron dose (1.5 g Fe/kg) in whole homogenates of both heart and liver (p < 0.01). We conclude that iron loading in this model profoundly alters the stability of hepatic and myocardial lysosomal membranes; furthermore, changes in serum glucosaminidase activity may be reflective of modified tissue lysosomal properties. Elevated levels of malondialdehyde in whole homogenates suggest that iron-mediated lipid peroxidation may be responsible in part for enhanced lysosomal membrane fragility.