Magnesium Sulfate Mitigates Lung Injury Induced by Bilateral Lower Limb Ischemia-Reperfusion in Rats

• Published in: The Journal of surgical research 2011-11, Vol.171 (1), p.e97-e106
• Main Authors: Kao, Ming-Chang, M.D, Jan, Woan-Ching, Ph.D, Tsai, Pei-Shan, Ph.D, Wang, Tao-Yeuan, M.D, Huang, Chun-Jen, MD, Ph.D
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - etiology; Acute Lung Injury - metabolism; Animals; Blood Gas Analysis; Blood Pressure - physiology; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - metabolism; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Extravascular Lung Water - metabolism; Heart Rate - physiology; Hindlimb - blood supply; IL-6; L-type calcium channels; Magnesium Sulfate - pharmacology; Male; MDA; MIP-2; Neutrophils - pathology; Nitric Oxide - metabolism; Oxidative Stress - drug effects; Peroxidase - metabolism; Pneumonia - drug therapy; Pneumonia - etiology; Pneumonia - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2011.03.028

Background Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO4 ) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO4 could mitigate I/R-induced lung injury. As MgSO4 is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. Materials and Methods Adult male rats were allocated to receive I/R, I/R plus MgSO4 (10, 50, or 100 mg/kg), or I/R plus MgSO4 (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 E2 concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO4 , 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 MgSO4. Conclusions MgSO4 mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.