The Mechanisms of Glutamine- and Fish Oil-Supplemented Resuscitation Fluids on Alleviating Oxidative Stress of the Lung and Liver in Rats with Trauma-Hemorrhagic Shock
Abstract Objectives Oxidative stress has been demonstrated to be the cause of cellular and organ damage in patients with trauma hemorrhagic shock and reperfusion (THR). Our previous study showed that resuscitation fluids supplemented with glutamine and fish oil, the antioxidants with anti-inflammatory activities, may alleviate systemic inflammatory response and oxidative stress in the THR rats. The aim of this study was to further investigate the mechanisms of these supplements on alleviating THR-induced damage in the lung and liver, i.e., the 2 vulnerable organs in THR. Methods Male Wistar rats were suffered with 5 cm midline laparotomy and 2 catheterizations in the left carotid artery and right jugular vein individually for blood drawn to a mean arterial pressure 30 to 35 mmHg for 60 minutes and for resuscitation of shed blood and lactate Ringer's solution with or without L-alanyl-L-glutamine (13.5 mmole/kg/day) and/or fish oil (0.5 g/kg/day) within 10 minutes. The different resuscitation fluids were continuous infused (∼1.4 ml/h) for 42 hr. Normal healthy rats and intubation sham-operated rats were included as controls. Results In the lung, the THR-increased lipid peroxidation and toll-like receptor 4 (TLR4) were significantly decreased by glutamine with or without fish oil (one-way ANOVA, P < 0.05). Fish oil was the main factor to decrease myeloperoxidase and activated caspase 3 in the lung of the THR rats (two-way ANOVA, P < 0.05). In the liver, the THR-increased lipid peroxidation and TLR4 and the THR-decreased catalase activity were improved by glutamine and/or fish oil. In addition, fish oil was the main factor to decrease inducible and endothelial nitric oxide synthase (NOS) and to increase IkB and phosphorylated NF-kB and glutamine was the main factor to decrease activated caspase 3 in the liver of the THR rats. Conclusions These results suggest that fish oil may alleviate neutrophil infiltration and NOS activation and fish oil and glutamine may elevate catalase activity and alleviate apoptosis to attenuate the THR-induced damage in the lung and liver. Funding Sources MOST 102-2320-B-030-005-MY3.