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Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

Salama SA, Omar HA, Maghrabi IA, AlSaeed MS, EL-Tarras AE.

Toxicol Appl Pharmacol. 2014 ;274(1):1-6.

High altitude research center, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia; Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751, Egypt; Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia; Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia; Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif, 21974, Saudi Arabia.

Abstract

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung  tissue injury  in rats  at high altitudes (6000ft above the sea level). Iron supplementation (2mg elemental iron/kg, once daily for 15days) induced histo-pathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1{Beta}, IL-6, and TNF-{Alpha}), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation  at high  altitudes  induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures.

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Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats