Cytotoxic aldehyde generation in heart following acute iron-loading

Although the mechanism of myocardial failure following acute iron poisoning is not known, excess iron-catalyzed free radical generation is conjectured to play a role. The effects of time (0 to 360 minutes) on total iron conce ntrations, glutathione peroxidase activity, and cytotoxic aldehyde producti on in heart of mice (B6D2F1, n =65) were first investigated following acute iron-loading (20 mg iron dextran i.p./ mouse). In a subsequent experiment, the effects of dose (0 to 80 mg iron dextran i.p. /mouse, n = 75) on the a forementioned parameters were investigated. Our results show that the conce ntrations of cytotoxic aldehydes: (1) significantly differ over-time, with corresponding increases in total concentrations of iron (r = 0.93, p < 0.00 1); and (2) increase parallel to the total dose of iron administered (r = 0 .95, p < 0.001). Furthermore, dose-and time-dependent alterations to glutat hione peroxidase activity are observed, which is most likely due to an acut e up-regulation of the enzyme as an endogenous protective response to incre ased free radical activity in the heart subsequent to iron-loading. While n o single mechanism is likely to account for the complex pathophysiology of acute iron-induced heart failure, our results shown that iron-loading can r esult in significant free radical generation, as quantified by cytotoxic al dehydes, in heart tissue of mice. This is the first report on the effects o f time and dose on cytotoxic aldehyde generation and glutathione peroxidase activity in heart of mice following acute iron-loading.