Antioxidant Mediated Effects in a Gerbil Model of Iron Overload.

Introduction: Iron cardiomyopathy is a lethal complication of monthly blood transfusion therapy in patients with thalassemia major. Medications or nutritional supplements that could potentially reduce cardiac iron uptake or toxicity would have clinical significance. The amino acid taurine is ubiquitous in both rodent and human myocytes, but its physiologic role is poorly understood. In mice, taurine supplementation decreases cardiac iron and oxidative toxicity. Since taurine could produce these effects through a direct antioxidant action or through modulation of iron uptake via calcium channels, we compared taurine’s benefits with a combination of vitamin E and selenium in the gerbil model of iron cardiomyopathy. We hypothesized that taurine supplementation would decrease cardiac iron levels and iron toxicity in a parallel manner while vitamin/selenium would only decrease cardiac iron toxicity.

Methods: Twenty-four animals were divided into four groups (control, iron, taurine, vitamin E + selenium). Supplementation was initiated 2 weeks prior to the iron loading period and continued throughout the 10 weeks of iron injection (200mg/kg/week). Taurine (12.5 g/L) and selenium (1.67g/L) were administered via drinking water, while vitamin E (400mg/gerbil/day) was injected subcutaneously daily. Post mortem assessment of heart and liver iron content, malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, aspartate aminotransferase (AST) levels, alanine transaminase (ALT) levels, histology, serum, and enzyme analyses were performed.

Results: No significant differences were found in heart and liver iron content between treatment groups, although dry-weight liver iron concentrations was increased in taurine-treated animals (p<0.03). Serum iron increased with iron loading (751 ± 66 ug/dL versus 251 ± 54 ug/dL, p < 0.001) and was further increased by taurine treatment (903 ± 136 ug/dL, p = 0.03). Iron overload increased cardiac malondialdehyde (MDA) levels and decreased heart and liver gluthathione peroxidase (GPx) activity, and increased serum AST consistent with oxidative stress. Taurine ameliorated these changes but results were significant only for liver GPx activity. Despite raising organ selenium levels, selenium and vitamin E supplementation did not improve oxidative markers (MDA, GPx) and actually worsened cardiac GPx levels.

Discussion: Prior murine work suggested selective cardioprotective effects of taurine mediated, in part, through decreased cardiac iron levels. In the gerbil model, taurine improved hepatic GPx, despite increasing liver iron concentration and serum iron. Qualitatively similar behavior was observed in the heart, but values did not reach statistical significance. Therefore, taurine exhibits antioxidant behavior that is not mediated by decreasing organ iron concentration; oxidative protection was superior to the effects produced by selenium/vitamin E supplementation. The etiology of the increased liver and serum iron concentrations is unclear but probably reflects interference with spontaneous iron losses. While taurine supplementation appears promising, future studies are needed to clarify interspecies variability in its behavior.