The Utility of Iron Chelators in the Management of Inflammatory Disorders

Table 1

Selected experimental studies.

Disease	Subject	Results	Reference
Cancer	Analysis of the specific murine OKT9-antibody on human leukemia cells	OKT9 receptor is transferrin; OKT9 binding on both normal and malignant cells was strongly associated with proliferation	[55]
	Expression of ferroportin and hepcidin in cultured human breast cancer cells plus an observational cohort study in patients	Reduction of ferroportin in cancer cells altered the labile iron pool; Combined ferroportin/hepcidin gene expression identified clinical subset of breast cancer	[58]
Atherosclerosis	Influence of zinc to the development of atherosclerotic plaques	Zinc fed rabbits showed decreased atherosclerotic plaques; Average lesion Fe levels in the zinc-fed group were significantly higher	[62]
	Effect of iron chelation on ferritin induction and iron accumulation in the rat aorta depending on Angiotensin II administration and vascular function	Angiotensin II infusion caused ferritin induction and iron deposition in the aortas; Impairment of vascular function was mediated in part by enhancement of oxidative stress	[63]
	Relationship between chronic hemolysis/increased body iron burden and premature atherosclerosis	Carotid intima-media thickness in patients with thalassemia major was significantly increased compared with healthy controls	[64]
Diabetes and Obesity	Role of iron in adiposity using diabetic and obese mice model (KKAy) DFO treatment	DFO diminished fat iron and serum ferritin levels, reduced fat weight and adipocyte size, and reduced macrophage infiltration, superoxide production, NADPH oxidase activity, and mRNA of inflammatory cytokines	[65]
	Effect of intravenous iron preparation on the beta cells in isolated pancreatic islets	Exposure to iron resulted in a concentration-dependent oxidative stress and pancreatic islet cell death predominantly affecting beta cells	[66]
Renal fibrosis	Effect of an iron chelator (DFO) on renal fibrosis induced by unilateral ureteral obstruction in mice	DFO suppressed changes including macrophage infiltration, expression of collagen and inflammatory cytokines, activation of the TGF-beta1/Smad3 pathway, and tubulointerstitial fibrosis	[67]
Glaucoma	To investigate the association between dietary and total calcium and iron consumption with a diagnosis of glaucoma	Odds of glaucoma were increased in the population with higher total consumption of calcium and iron	[68]
	To study the effect of metal chelator EDTA on the rat optic nerve and retinal ganglion cells exposed to oxidative stress	EDTA ameliorated oxidative damage and inflammation, increased survival of retinal ganglion cell, and decreased demyelination of optic nerve	[69]
Systemic inflammatory response syndrome	To study the effect of DFO on acute hepatic ischemia induced SIRS in pigs	DFO completely blocked IL-6 production and lipid peroxidation and attenuated the development of SIRS and MOD	[70]
	To study the effect of DFO on acute hepatic ischemia induced SIRS in swine	DFO inhibited iron-catalyzed oxidative reactions, delayed the development of intracranial hypertension, and improved survival	[71]
	To test the hypothesis that inhibition of oxidative stress through iron chelation with DFO attenuates pulmonary injury caused by acute liver failure (ALF)	DFO reduced systemic and pulmonary oxidative stress during ALF, attenuated pneumonocyte necrosis, improved alveolocapillary membrane permeability, and prevented alveolar space collapse	[72]
Colitis	To evaluate the effect of selected iron chelators and antioxidants on protection of trinitrobenzene sulfonic acid (TNBS) induced colitis in rats	Maltol (iron chelator) was capable of protecting rat from TNBS induced colitis; Kojic acid (iron chelator) and vitamin E (antioxidant) were not effective	[73]