Chun-Yi Lee1, Woan-Ching Jan, Pei-Shan Tsai, Chun-Jen Huang. 1. Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, and Department of Nursing, Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
Abstract
BACKGROUND: Magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. We sought to elucidate the effects of MgSO4 on mitigating acute lung injury induced by endotoxemia. MgSO4 is an antagonist of the L-type calcium channels and the N-methyl-D-aspartate (NMDA) receptor. The roles of the L-type calcium channels and NMDA receptor in this regard were also elucidated. METHODS: Ninety-six adult male rats were randomized to receive normal saline, MgSO4 (100 mg/kg), lipopolysaccharide (LPS), LPS plus MgSO4 (10, 50, or 100 mg/kg), LPS plus MgSO4 (100 mg/kg) plus the L-type calcium channel activator BAY-K8644, or LPS plus MgSO4 (100 mg/kg) plus exogenous NMDA (n=12 in each group). Between-group differences in lung injury were evaluated. RESULTS: Histologic findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that LPS induced acute lung injury. LPS also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E2 concentrations) and imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations) in rat lungs. MgSO4 at the dosages of 50 mg/kg and 100 mg/kg, but not at 10 mg/kg, significantly mitigated the acute lung injury, lung inflammatory response, and oxidative stress caused by endotoxemia. Moreover, the protective effects of MgSO4 were counteracted by BAY-K8644 and exogenous NMDA. CONCLUSIONS: MgSO4 mitigates lung inflammatory response, oxidative stress, and acute lung injury in endotoxemia rats in a dose-dependent manner. The mechanisms may involve antagonizing the L-type calcium channels and the NMDA receptor.
BACKGROUND:Magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. We sought to elucidate the effects of MgSO4 on mitigating acute lung injury induced by endotoxemia. MgSO4 is an antagonist of the L-type calcium channels and the N-methyl-D-aspartate (NMDA) receptor. The roles of the L-type calcium channels and NMDA receptor in this regard were also elucidated. METHODS: Ninety-six adult male rats were randomized to receive normal saline, MgSO4 (100 mg/kg), lipopolysaccharide (LPS), LPS plus MgSO4 (10, 50, or 100 mg/kg), LPS plus MgSO4 (100 mg/kg) plus the L-type calcium channel activator BAY-K8644, or LPS plus MgSO4 (100 mg/kg) plus exogenous NMDA (n=12 in each group). Between-group differences in lung injury were evaluated. RESULTS: Histologic findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that LPS induced acute lung injury. LPS also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E2 concentrations) and imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations) in rat lungs. MgSO4 at the dosages of 50 mg/kg and 100 mg/kg, but not at 10 mg/kg, significantly mitigated the acute lung injury, lung inflammatory response, and oxidative stress caused by endotoxemia. Moreover, the protective effects of MgSO4 were counteracted by BAY-K8644 and exogenous NMDA. CONCLUSIONS:MgSO4 mitigates lung inflammatory response, oxidative stress, and acute lung injury in endotoxemiarats in a dose-dependent manner. The mechanisms may involve antagonizing the L-type calcium channels and the NMDA receptor.