title: Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats.
abstract: BACKGROUND
  Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated.
  
  
  METHODS
  Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined.
  
  
  RESULTS
  Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4).
  
  
  CONCLUSIONS
  MgSO(4) mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.
authors.affiliation: Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Kao
authors.forename: Woan-Ching
authors.initials: WC
authors.lastname: Jan
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Tao-Yeuan
authors.initials: TY
authors.lastname: Wang
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015633:Extravascular Lung Water / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009569:Nitric Oxide; D008278:Magnesium Sulfate; D009195:Peroxidase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone