First human studies with a high-molecular-weight iron chelator.

The release of free, reactive iron from cellular iron stores has been implicated as an important contributor to tissue damage in a variety of clinical situations, including ischemia and reperfusion injury, hemorrhagic shock, and burn injury. Deferoxamine mesylate (DFO), the only iron chelator currently approved for clinical use, is used for the treatment of iron overload, including acute iron poisoning and treatment of chronic iron overload in transfusion-dependent anemias such as beta-thalassemia. However, it is not suitable for acute care situations because of its toxicity, primarily hypotension when given at high intravenous doses, and its short plasma half-life.

The long-acting parenteral iron chelator, hydroxyethyl starch-deferoxamine, fails to protect against alcohol-induced liver injury in rats.

We studied the effect of the long-acting parenteral iron chelator, hydroxyethyl starch deferoxamine (HES-DFO) on liver nonheme iron, lipid peroxidation and pathologic changes in the liver in the intragastric feeding rat model for alcoholic liver disease. Male Wistar rats (225-250 g) were fed liquid diet and ethanol for 2 months. In control pair-fed animals, ethanol was isocalorically replaced by dextrose.

Polymer conjugation reduces deferoxamine induced retinopathy in an albino rat model.

Purpose: The iron chelating agent deferoxamine mesylate USP (Desferal, Ciba, Summit, NJ) is commonly used in the treatment of acute iron intoxication and chronic iron overload (associated with the transfusion-dependent anemias). When used for prolonged periods of time or in high doses deferoxamine is attended by a range of ocular toxicities. The visual symptoms associated with deferoxamine administration often limit effective iron chelation therapy and can result in permanent vision loss.

Role of iron and oxygen radicals in hemorrhage and shock.

This contribution focuses on the role of iron as a critical component in the genesis of oxygen radical mediated tissue injury occurring after global ischemia associated with severe hypovolemic shock. Conventional colloid or crystalloid fluid resuscitation does not adequately protect organs susceptible to reperfusion injury. One approach aimed at attenuating such post-trauma reperfusion injury is systemic, high dose, iron chelation used in combination with colloid fluid replacement.