The intimate relationship between Fe and Cu in human nutrition has been recognised for many years. The best-characterised link is provided by caeruloplasmin, a multiCu-binding protein that acts as a serum ferrioxidase and is essential for the mobilisation of Fe from storage tissues. Decreased Cu status has been shown to reduce holo-caeruloplasmin production and impair ferrioxidase activity, leading, in a number of cases, to decreased tissue Fe release and the generation of anaemia that is responsive to dietary supplementation with Cu but not Fe. Dietary Fe absorption also requires the presence of a multiCu ferrioxidase. Hephaestin, a caeruloplasmin homologue, works in concert with the IREG1 transporter to permit Fe efflux from enterocytes for loading onto transferrin. The essential role of hephaestin in this process has been recognised from studies in the sex-linked anaemic (sla) mouse, in which Fe efflux is markedly impaired as a result of a mutation in the hephaestin gene that results in a truncated and non-functional version of the protein. There is emerging evidence that a number of other components of the intestinal Fe transport pathway are also Cu sensitive. Divalent metal transporter 1 (DMT1), the Fe transporter located at the apical membrane of enterocytes, is also a physiologically-relevant Cu transporter, suggesting that these two metals may compete with each other for uptake into the duodenal enterocytes. Furthermore, expression of both DMT1 and the basolateral Fe-efflux transporter IREG1 can be regulated by Cu, suggesting that the Fe–Cu relationship may be more complex than first thought.

Exercise is associated with an increase in the production of oxidants that may be instrumental in the development of exertional rhabdomyolysis. We speculated that participation in a long-distance sled race would alter antioxidant capacity of dogs, in conjunction with increases in indices of rhabdomyolysis. The objective was to determine the effect of participation in a long-distance sled dog race on antioxidant capacity and plasma creatine kinase (CK) activity in sled dogs. This was a prospective, longitudinal study on a convenience sample of 57 Alaskan sled dogs participating in a 1600 km sled dog race. Blood samples were collected before racing (31 dogs) and after racing (39 dogs) for measurement of plasma vitamin E concentration; CK, aspartate aminotransferase (AST) and caeruloplasmin (CER) activity; and red-blood-cell (RBC) glutathione peroxidase (GPX) and superoxide dismutase (SOD) activity. CER and GPX activities after the race were 26% and 14% lower, respectively, than before racing whereas CK and AST were 300% and 170% greater. There was no change in plasma vitamin E concentration or RBC SOD activity. We conclude that completion of a long-distance sled dog race involving prolonged and repeated submaximal exercise results in a reduction in enzymatic antioxidant activity in the blood of sled dogs.