Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats.
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 histopathological 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-1β, IL-6, and TNF-α), 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 7days 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.
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. Electronic address: salama.3@buckeyemail.osu.edu.
Samir A
SA
Salama
Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Hany A
HA
Omar
Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974, Saudi Arabia.
Ibrahim A
IA
Maghrabi
Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974, Saudi Arabia.
Mohammed S
MS
AlSaeed
High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974, Saudi Arabia.
Adel E
AE
EL-Tarras
D000531:Altitude; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002839:Chromans / Q000627:therapeutic use; D019587:Dietary Supplements / Q000633:toxicity*; D007501:Iron / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D017382:Reactive Oxygen Species; D007501:Iron; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
2,4-dinitrophenyl hydrazine; 5,5′-dithiobis (2-nitrobenzoic acid); DNPH; DTNB; ETC; GSH; H&E; HIFs; High altitudes; IL-1β; IL-6; Iron supplementation; Lung tissue injury; MDA; Oxidative stress; PBS; Proinflammatory cytokines; RNS; ROS; TAC; TBARS; TCA; TNF-α; Trolox; electron transport chain; hematoxylin and eosin; hypoxia inducible factors; interleukin-1β; interleukin-6; malondialdehyde; phosphate buffered saline; reactive nitrogen species; reactive oxygen species; reduced glutathione; thiobarbituric acid reactive substances; total antioxidant capacity; trichloroacetic acid; tumor necrosis factor-α