Actually, in an animal model of diabetes mellitus, such as Sprague-Dawley rats treated with streptozotocin, HO-1 downregulation increased both superoxide anion formation in aortas and urinary 8-epi-isoprostane PGF2α, whereas the upregulation significantly counteracted oxidative damage, as demonstrated by the reduction in these local and systemic biomarkers [177]. This evidence concerns the gene HMOX1 and diabetes mellitus.