Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma — a review
1Emergency County Hospital Timisoara, Clinic of Anesthesia and Intensive Care, Timisoara, Romania
2“Victor Babes” University of Medicine and Pharmacy Timisoara, Faculty of Medicine, Timisoara, Romania
3West University of Timisoara, Faculty of Chemistry, Biology, Geography, Timisoara, Romania
4Emergency County Hospital Timisoara, Clinic of Anesthesia and Intensive Care “Casa Austria”, Timisoara, Romania
5 University of Essex, Economics Department, Essex, United Kingdom
Multiple trauma patients require extremely good management and thus, the trauma team needs to be prepared and to be up to date with the new standards of intensive therapy. Oxidative stress and free radicals representan extremely aggressive factor to cells, having a direct consequence upon the severity of lung inflammation.
Pulmonary tissue is damaged by oxidative stress, leading to biosynthesis of mediators that exacerbate inflammation modulators. The subsequent inflammation spreads throughout the body, leading most of the time to multiple organ dysfunction and death.
In this paper, we briefly present an update of biochemical effects of oxidative stress and free radical damage to the pulmonary tissue in patients in critical condition in the intensive care unit. Also, we would like to present a series of active substances that substantially reduce the aggressiveness of free radicals, increasing the chances of survival.
Keywords: lung injury, inflammation; oxidative stress, antioxidant therapy; multiple trauma; critically ill patient
Anestezjologia Intensywna Terapia 2015, tom XLVII, nr 4, 365–373
Należy cytować wersję:
Bedreag OH, Rogobete AF, Sarandan M et at: Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma — a review. Anaesthesiol Intensive Ther 2015; 47: 351–359. 10.5603/AIT.a2015.0030.
Multiple trauma patients are, and will always be, a challenge for the intensive care unit (ICU) [1, 2]. Most often, patients with multiple traumas develop serious lung problems due to several complications arising from injury, infections or from mechanical ventilation. The management of the respiratory system has a special importance , due to the constantand critical need of tissue oxygenation ofthe body [3–6]. Recorded data in Trauma Register DGU (Germany) , and presented by Huber et al. , highlight a high mortality rate with pulmonary trauma patients: 17.5% (16.5% male and 20.5% female). In retrospective group studies (2002–2011) patients with an ISS score higher than 16.48% were patients who have suffered lung contusion, out of which, 39% pneumothorax, 28% hemothorax, 12% lung lacerations, 3% thoracic vessel injuries .
Acid-base imbalances , low oxygenation  and cellular death  are just some ofthe complications of a deficient respiratory system, that lead to multiple organ damage .
In turn, the pulmonary tissue is affected by injuries, inflammations (Systemic Inflammatory Response Syndrome — SIRS), and infections (Acute Respiratory Distress Syndrome — ARDS, Ventilator-Associated Pneumonia — VAP) . Together, those clinical aspects accelerate biochemically the production offree radicals with devastating effects for the cell and by default for the whole biological system [12–14]. Thus, this stimulates the so-called ‘oxidative stress’ [15, 16], which has a significant contribution in the clinical status of the patient. Pulmonary dysfunction leads to a series of complications that make recovery impossible  through the activation of the hyper-metabolism induced by severe trauma.
In this paper, we propose an update to the action of free radicals and oxidative stress on the pulmonary tissue in patients with multiple traumas and also an update to the current research concerning therapy with antioxidants.
BIOCHEMICAL ASPECTS OF FREE RADICALS AND THE ACTIONS OF OXIDATIVE STRESS
Biochemical reactions that take place in cells are all driving forces that sustain life . In physiological conditions, oxygen is used by our body for cellular respiration, defence, detoxification and embryonic development. Due to physiological imbalance or traumas, the oxygen is transformed in non-physiological species, which aretoxicforthe body and are called free radicals. Free radicals are unstable molecules, ions or clusters of atoms, with an extremely high reactivity toward molecules around them [17–22].
The oxidative stress affects mainly the cellular organelles . These alterations of physiological functions are caused by extremely reactive free radical compounds that influence enzymatic and membrane activities. The extremely high reactivity of these free species becomes very important when it comes to the study of tissue complications, especially in the case of patients with multiple trauma, when because of the significant injuries, the patient develops hyper-metabolism [24, 25]. The biochemical alterations at the cellular level imply oxidative reactions of the DNA, structural modifications of the proteins and oxidative modifications of lipids  (Fig. 1).
Reactive oxygen species are produced in high quantities through endogenous metabolisms , while at the same time, there are also a large class of exogenous factors that increase the production of free radicals. Such mechanisms that can generate free radicals inside the body are represented by: the activation of neutrophils, the electron transport chain at the mitochondrial level, arachidonic acid metabolism, oxide-reduction of xanthine  or nitric oxide synthesis [27, 29–31]. The respiratory chain [32–34] has a key role atthe cellular level, being responsible forthe conversion of oxygen in water molecules. At the neutrophils’ level, the major source of oxygen is the enzymatic complex NAD(P) H oxidase. Moreover, severe infections of the pulmonary tissue can lead to massive synthesis of reactive species of oxygen and accumulation. The enzymatic processes that take partin the defence of the tissues transform a part of the oxygen in reactive species that lead to tissue inflammation . In the pulmonary tissue, the most important source or free radicals are the neutrophils, eosinophils, leucocytes or different enzyme modulators .
The biochemical process activities lead to the overproduction of inflammatory molecules with immediate response on inflammation spreading [37, 38]. Chang et al. suggest that in this case proteoglycans have a determinant role, since they are responsible for the response given by the aggression . The level of inflammatory mediators determines the level of inflammatory response . The endotoxin, the activation of the complement, the cytokines, the arachidonic acid’s metabolites, liposomal enzymes and kinines, histamine, the nitric oxide or the mediators derived from the endothelium, are the aggressive participants in the decompensation of the patient’s clinical status. The complications arise together with micro-embolisms, pulmonary artery hypertension and the alteration of the respiratory functions [41–48]. Neutrophils stimulation through different biochemical mechanisms produces high quantities of hydrogen peroxide [49–51]. The biosynthesised oxidants have a role in destroying bacteria, but the adverse effects produce a series of tissue inflammations. The accumulation of neutrophils and the exacerbated biosynthesis of inflammatory cytokine, combined with the ICU conditions (VAP, SEPSIS, etc.) lead to a severe destruction of the pulmonary tissue [51–53]. Active oxygenated species,and implicitly oxidative stress, affects the lung, especially through lipid peroxidation, the increased production of pro-inflammatory molecules, protein oxidation and inactivation of antioxidants . The abnormal oxidation of proteins from the pulmonary tissue that is made possible by the compounds of the oxidative stress is directly implicated in the pathogenesis of a series of pulmonary diseases. The lipid oxidation is associated with the generation of a big number of toxic compounds with direct and severe implications in the destruction of cells through membrane damage, inhibition of the biochemical processes of the cell and in the end its death [55–58].
A lung injury is often brought by the oxygen therapy — hyperoxia induced by mechanical ventilation in the management of severe respiratory dysfunctions [25, 59–61]. There are a series of controversies related to the parameters used in mechanical ventilation, especially when we are talking aboutan inflammated lung. The severe pulmonary destruction and inflammation can have severe consequences at a patient with multiple trauma, the majority leading to Multiple Organ Dysfunction Syndrome (MODS) [62, 63] and death [64–66].
Many critically ill patients are being brought in the emergency units in haemorrhagic shock [67, 68]. Inadequate resuscitation and the complications that may arise in this case, makes the recovery of the patient hard or impossible [69–71]. An aggressive and inadequate fluids resuscitation can produce high quantities of reactive species of oxygen through the re-oxygenatlon of the tissue . Once the tissue’s reperfuslon takes place, an important source of reactive oxygen appears, the main biosynthesis being xanthone-oxydaze reactions. For this matter, a series of active compounds [72–75] that can reduce the inflammations resulting from the fluids generated by resuscitation have been studies. The compounds that had a great contribution in the good post-resuscitation management are acid valproic , or N-acetylcysteine . The complete impact of the oxidative stress and free radical on the pulmonary tissue and the biochemical and physiological explications of all the clinical manifestation that appear In a patient with multiple traumas remain unclear and need further research.
THERAPY WITH ANTIOXIDANTS
Destructive effects of free radicals and oxidative stress are mlnlmallzed naturally by the organism through the defensive antioxidant system. The antioxidants are compounds that inhibit or slow down the oxidative damage [76–78] brought to a molecule by a free radical [79–81]. The antioxidants react in various ways  — inhibitors of the oxidative reaction determined by free radicals, saturation with oxygen singlet, blocking the chain of oxidative reactions, transforming hydroxyl-peroxides in stable compounds. Inhibiting some pro-oxidative enzymes orthrough synergy with other antioxidants [77, 83–86] (Table 1).
Table 1. Substances with antioxidant capacity
|Ribeiro et al.||CANNABIDIOL||Antioxidant effects|||
|Reduce lung inflammation|
|Attenuation of acute lung injury|
|20 mg kg-1 —1 single dose|
|Benetti et al.||SULPHURED HYDROGEN||Inhibits the acumulation of neutriphiles|||
|Activates the production of enzimatic engoden antioxidants|
|Wu et al.||EICOSAPENTAENOIC AICD||Reduces cellular apoptosis|||
|Modulates mitochondrial activity|
|Santos et al.||OLEANIC ACID||Strong antioxidant properties|||
|Administration intra-peritoneal injection|
|Choi et al.||DESOXYRHAPONTIGENIN||Modulates cytokine biosynthesis|||
|Torres et al.||METHYLPREDNISOLONE||Positive effects in inflammation and sepsis|||
|Slows down the oxidative damage|
|Activation of antioxidative enzymes|
|Kutsukake et al.||PIOGLITAZONE||Significantly reduces the concentration of IL-6, TNF-α|||
|Blocks haemocyte infiltration|
|Significant positive effects in acute lung injury|
|Straaten et al.||VITAMIN C||Modulates antioxidant enzyme activity|||
|Blocks the production of free radicals|
|Reduce the stationing in ICU|
|Protects lung tissue from biochemical injuries cause by oxidative stress|
|Wischmeyer et al.||GLUTAMINE||Reduces the level of oxidative stress biomarkers|||
|Significantly reduces mortality|
|Ayvaz et al.||METHYLENE BLUE||Positive effects in sepsis|||
|Positive effects in lung injury|
|Significantly reduces lung tissue injuries|
|Qin et al.||ULI STATIN||Reduces considerably the systemic effects of the inflammation|||
|Reduces significantly the complications that can arise from lung injuries|
|Reduces the effects of free radicals|
|Liu et al.||SALIDROSIDE||Reduces the plasmatic concentration of TNF-α, IL-6 and IL-1|||
|Blocks the specific receptors — peroxisome proliferator|
The body has such anti-oxidative compounds, naturally — anti-oxidative enzyme (glutathionperoxidase, catalase or superoxide-dismutase) [86, 87], metals or other compounds chelation agents (coenzyme, vitamin, acid uric, peptide, Cu, Zn etc.) [88–90]. The cellular membrane is protected by the attack of the oxidative stress by ubiquinone, which can be found in high quantities in the Golgi mechanism and in the liposomal membranes [91, 92]. Nowadays, intensive research is being done on a series of blologically-active substances that can minimize and even block the mechanisms that biosynthesise free radicals, in ordertoavoid pulmonary tissue complications. It is known both scientifically and practically that the loss of control of the pulmonary infections or inflammations is directly linked with the spreading of these to the rest of the body which result in true physiological and pathological catastrophes.
Ribeiro et al.  studied the effect of cannabidiol on severe pulmonary tissue affections on laboratory rats. They emphasised the anti-inflammatory potential of this compound, demonstrating the beneficial effects brought by the reduction of lung injury when the inflammatory process has already evolved in the patient, and thus demonstrating the ability of the compound to be effective even if the lung is already inflammated.
In many scientific papers the beneficial effect of the sulphureted hydrogen on the inflammated lung is presented [88, 93–97]. Benetti et al.  demonstrates that through the administration of the sodium mono-hydrogen-sulphate (NaHS) that generates sulphureted hydrogen, the accumulation of neutrophils and of eosinophils is inhibited.
Elcosapentaenoic acid — enriched phospholipids extracted from sea cucumber Cucumariafrondosa, also has an inhibition effect on the reactive oxygenated species [89, 98–105]. Wu et al.  remarks that this antioxidant compound alters the metabolic way of the mitochondrial apoptosis .
Santos et al.  demonstrated that the intra-peritoneal injection of oleanolic acid at one hour after the lung injury controls the oxidative and inflammatory process, while avoiding important modification from a physiological and histological point of view.
The endotoxin responsible for the tissue inflammation and the pro-inflammatory effects of the reactive oxygenated species [106–109] are inhibited by another compound called desoxyrhapontlgenln , which is recommended by Choi et al. to be used for its anti-oxidative and anti-inflammatory properties . Other studies recommend the use of small quantities of corticosteroids for long periods of time (1–2 mg kg-1 day-1) . Those reduce considerably the systemic effects of the inflammation. Ayvaz et al.  demonstrate in their study on laboratory animals that intravenous administration of 2 mg kg-1 of methylene blue reduces considerably the quantity of nitric oxide, endothelial nitric oxide synthase. Furthermore they observed positive effects on lung tissue ischemia reperfusion damage.
A study on laboratory mice by Torres et al. , demonstrates that the administration of methylprednisolone  activates the antioxidant compounds of the pulmonary tissue. The association of ploglltazone in patients’ therapy in ICU reduces significantly the complication that can arise from lung injuries. These effects have been studied by Kutsukake et al. , demonstrating that through the administration of this active compound the tumour necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) concentrations (Fig. 2) are significantly reduced, and also haemocyte infiltration, inflammation and cellular death is reduced (Fig. 3) . The levels of pro-inflammatory cytokines that are released uncontrollably in the pulmonary tissue are also inhibited by ulistatin  or salidroside . The beneficial effects of these active compounds on the reduction of plasmatic concentrations of TNF-α, IL-6 si IL-1 [30,110] have been demonstrated and studied. Salidroside inhibits the inflammatory response by blocking the specific receptors — peroxisome prollferator — activated receptors (PPAR-γ) .
Glutamine, is the most abundant unessential amino acid. Its antioxidant proprieties are intensely studied. Numerous beneficial proprieties that this aminoacid brings to critically ill patients due to its effect on cellular defence pathways, modulation of the inflammatory response and prevention of organ injuries cause by free radicals  were discovered. The administration of glutamine in pulmonary Infections reduces, according to studies, reduce hospital mortality and retention time in the ICU. Wischmeyer et al. , in their study regarding the administration of glutamine on critical patients report that intravenous administration of 0,3–0,5 g kg-1 day-1 significantly improves the clinical status of the patients.
Straaten et al.  report the Importance of administration of vitamin C in critical patients. Numerous studies show that vitamin C reduces considerably the production of free radicals. Furthermore, in sepsis activates the action of macrophages, regulates the production of cytokines, modulates the inflammatory response, reduces neutrophil oxidative burst and regulates the antioxidant-oxidant balance. Administration of doses of vitamin C varies depending on the case, but in many articles it’s recommended an intake of 1000-–1500 mg day-1 of vitamin C intravenously for 3–5 days .
Another antioxidant remedy that was reported in specialized studies is omega 3 fatty acids. Numerous beneficial effects of these active substances were shown especially in critically ill patients with lung trauma — ARDS, sepsis. Administration on entirely path of supplements with a high omega 3 fatty acids reduce mortality with 19 % according to studies [113, 114].
Other compounds with remarkably good anti-oxidative and anti-inflammatory effects have been studied for the purpose of reducing the inflammatory effects of the oxidative stress on pulmonary tissue, among which pentoxifylline , apocynin-nitrone , narginin , sphingisylphosphorylcholine , usnic acid , zinc aspartate , trapidil  or melatonin .
A critically ill patient suffers a series of complications due respiratory problems. The pulmonary tissue becomes inflammated due to infections, trauma or genetic determinism, which induces in the end the spreading of the inflammation and multiple organ death. The conditions of the intensive therapy — nursing, the lavage of endotracheal intubation tube, or the mechanical ventilator — lead as well to complications in the lungs, sometimes provoking important injuries. The extracellular membranes are damaged through the action of free radicals, forming toxic compounds that have a crucial impact on the physiological status of the lung, accelerating the destructive inflammatory processes.
Oxidative stress and free radicals contribute directly to the degradation of the physiological state of the pulmonary tissue, complicating the management of the patient with multiple traumas. Current research offers a series of alternatives that minimizes the adverse effects of the oxidative stress on the pulmonary tissue. The protocollzatlon of antioxidant therapy and the investigation of biomarkers responsible for oxidative stress becomes a necessity, being useful in minimization of inflammatory effects caused by free radicals.
In conclusion, it can be affirmed that a serious thought should be given when considering these aspects of oxidative stress on the lung. Severe complications thatarlse due to severe inflammations, infections or a partially-working lung can only substantially or completely reduce the chances of survival in ICU. We conslderthat current research regarding intensive care in multiple trauma cases for reduction of pulmonary, and implicitly systemic. Inflammation and infection are extremely important nowadays and should be taken into consideration. Our paper’s limitations are given by the lack of presentation of all compounds that have antioxidant properties and that are used in the control of pulmonary and tissue inflammations for patients that are in a critical state.
- The authors declare no finadal disclosure.
- The authors declare no conflict of interest.
- Teranishi K, Scultetus A, Haque A, Stem S, Philbin N, Rice J et al.:Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre-hospital resuscitation in a swine model. Injury 2012; 43: 585–593. doi: 10.1016/j.injury.2010.09.042.
- Schilero GJ, Spungen AM, Bauman WA, Radulovic M, Lesser M: Pulmonary function and spinal cord injury. Respir Physiol Neurobiol 2009; 166: 129–141. doi: 10.1016/j.resp.2009.04.002.
- Golder FJ, Hewitt MM, McLeod JF: Respiratory stimulant drugs in the post-operative setting. Respir Physiol Neurobiol 2013; 189: 395–402. doi: 10.1016/j.resp.2013.06.010.
- Doerr CH, Gajic O, Berrios JC et al.: Hypercapnic acidosis impairs plasma membrane. Wound Resealing in Ventilator-injured Lungs. Am J Respir Crit Care Med 2005; 171: 1371–1377. doi: 10.1164/rccm.200309-12230C.
- Alkhouri H, Poppinga WJ, Tania NP, Ammit A, Schuliga M: Regulation of pulmonary inflammation by mesenchymal cells. Pulm Pharmacol Ther 2014; 29: 156–165. doi: 10.1016/j.pupt.2014.03.001
- Huber S, Biberthaler P, Delhey P et al.: Predictors of poor outcomes after significant chest trauma in multiply injured patients: a retrospective analysis from the German Trauma Registry (Trauma Register DGU®). Scand J Trauma Resusc Emerg Med 2014; 22: 52. doi: 10.1186/s13049014-0052-4.
- Hopper K, Haskins SC: The acid-base effects of free water removal from and addition to oxygenated and deoxygenated whole blood an in vitro model of contraction alkalosis and dilutional acidosis. Transl Res 2011; 157: 29–37. doi: 10.1016/j.trsl.2010.09.006.
- Boerma EC, Ince C: The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients. Intensive Care Med 2010; 36: 2004–2018. doi: 10.1007/s00134010-1970-x.
- Hossmann K-A: Pathophysiology and therapy of experimental stroke. Cell Mol Neurobiol 2006; 26: 1057–1083. doi: 10.1007/s10571-0069008-1.
- Arlati S, Storti E, Pradella V, Bucci L, Vitolo A, Puiici M: Decreased fluid volume to reduce organ damage: a new approach to burn shock resuscitation? A preliminary study. Resuscitation 2007; 72: 371–378. doi: http://dx.doi.Org/10.1016/j.resuscitation.2006.07.010.
- Arroyo V, Garcia-Martinez R, Salvatella X: Human serum albumin, systemic inflammation, and cirrhosis. J Hepatol 2014; 61: 396–407. doi: 10.1016/j.jhep.2014.04.012.
- Pirchl M, Ullrich C, Sperner-Unterweger B, Humpel C: Homocysteine has anti-inflammatory properties in a hypercholesterolemic rat model in vivo. Mol Cell Neurosci 2012; 49: 456–463. doi: 10.1016/j.mcn.2012.03.001.
- Huang Y, Yan B, Yang Z: Clinical study of a formula for delayed rapid fluid resuscitation for patients with burn shock. Burns 2005; 31: 617–622. doi: http://dx.doi.Org/10.1016/j.burns.2005.02.002.
- Do Lago LCC, Matias AC, Nomura CS, Cerchiaro G: Radical production by hydrogen peroxide/bicarbonate and copper uptake in mammalian cells: modulation by Cu(II) complexes. J Inorg Biochem 2011; 105: 189–194. doi: 10.1016/j.jinorgbio.2010.10.017.
- Takasu A, Shibata M, Uchino S, Nishi K, Yamamoto Y, Sakamoto T: Effects of arterial oxygen content on oxidative stress during resuscitation in a rat hemorrhagic shock model. Resuscitation 2011; 82:110–114. doi: 10.1016/j.resuscitation.2010.10.007.
- Hohl A, Gullo JDS, Silva CCP et al.: Plasma levels of oxidative stress biomarkers and hospital mortality in severe head injury: a multivariate analysis. J Crit Care 2012; 27: 523.e11–9. doi: 10.1016/j.jcrc.2011.06.007.
- Gottfredsen RH, Larsen UG, Enghild JJ, Petersen SV: Redox Biology Hydrogen peroxide induce modifications of human extracellular superoxide dismutasethat results in enzyme inhibition. Redox Biol 2013; 1: 24–31. doi: 10.1016/j.redox.2012.12.004.
- Steele ML, Fuller S, Patel M, Kersaitis C, Ooi L, Munch G: Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells. Redox Biol 2013; 1: 441–445. doi: 10.1016/j.redox.2013.08.006.
- Moraes I, Evans G, Sanchez-Weatherby J, Newstead S, Shaw PD: Biochimica et biophysica acta membrane protein structure determination — the next generation. BBA — Biomembr 2014; 1838: 78–87. doi: 10.1016/j.bbamem.2013.07.010.
- Tinti F, Soory M: Oxidative actions of hydrogen peroxide in human gingival and oral periosteal fibroblasts: Responses to glutathione and nicotine, relevant to healing in a redox environment. Redox Biol 2013; 2:36–43. doi: 10.1016/j.redox.2013.11.008.
- Carvalho-Silva LB, Oliveira V, Silva V et al.: Antioxidant, cytotoxic and antimutagenic activities of 7-epi-clusianone obtained from pericarp of Garcinia brasiliensis. FRIN 2012; 48: 180–186. doi: 10.1016/j.foodres.2012.03.003.
- Zampetaki A, Dudek K, Mayr M: Oxidative stress in atherosclerosis: the role of microRNAs in arterial remodeling. Free RadicBiol Med 2013; 64: 69–77. doi: 10.1016/j.freeradbiomed.2013.06.025.
- Kim H, Bae S, Kim Y et al.: Vitamin C prevents stress-induced damage on the heart caused by the death of cardiomyocytes, through down-regulation of the excessive production of catecholamine, TNF-α, and ROS production in Gulo(–/–) Vit C-insufficient mice. Free Radic Biol Med 2013; 65: 573–583. doi: 10.1016/j.freeradbiomed.2013.07.023.
- Tkaczyk J, Vízek M: Oxidative stress in the lung tissue — sources of reactive oxygen species and antioxidant defence. Prague Med Rep 2007; 108: 105–114.
- Bansal S, Biswas G, Avadhani NG: Mitochondria-targeted heme oxygenase-1 induces oxidative stress and mitochondrial dysfunction in macrophages, kidney fibroblasts and in chronic alcohol hepatotoxicity. Redox Biol 2014; 2: 273–283. doi: 10.1016/j.redox.2013.07.004.
- Kaur SAP, Guggenheim EJ, Pulisciano C, Akbar S, Kershaw RM, Hodges NJ: Cellular accumulation of Cys326-OGG1 protein complexes under conditions of oxidative stress. Biochem Biophys Res Commun 2014; 447: 12–18. doi: 10.1016/j.bbrc.2014.03.044.
- Kalogeris T, Bao Y, Korthuis RJ: Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol 2014; 2: 702–714. doi: 10.1016/j.redox.2014.05.006.
- Bretón-Romero R, Lamas S: Hydrogen peroxide signaling in vascular endothelial cells. Redox Biol 2014; 2: 529–534. doi: 10.1016/j.redox.2014.02.005.
- Patra MK, Kumar H, Nandi S: Neutrophil functions and cytokines expression profile in buffaloes with impending postpartum reproductive disorders. Asian-Australasian J Anim Sci 2013; 26: 1406–1415. doi: 10.5713/ajas.2012.12703.
- Douzinas EE, Betrosian A, Giamarellos-Bourboulis EJ et al.: Hypoxemic resuscitation from hemorrhagic shock prevents lung injury and attenuates oxidative response and IL-8 overexpression. Free Radie Biol Med 2011, 50: 245–253. doi: 10.1016/j.freeradbiomed.2010.10.712.
- Kwon OY, Lim SG, Park SH: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode leading to recurrent superior mesenteric artery syndrome. Am J Emerg Med 2014; 32: 951.e1–2. doi: 10.1016/j.ajem.2014.01.059.
- Park J, Nam H, Ahn SY, Pak YK, Pak JJ: A reservoir-type oxygen sensor with 2×3 array for measuring cellular respiration levels. Sensors Actuators B Chem 2013; 176: 913–920. doi: http://dx.doi.Org/10.1016/j. snb.2012.09.037.
- Yip N-C, Rawson EJ, Tsang GW, Mendes PM: Real-time electrocatalytic sensing of cellular respiration. Biosens Bioelectron 2014, 57: 303–309. doi: 10.1016/j.bios.2014.01.059.
- Rosenfeld M, Brenner-Lavie H, Ari SG-B, Kavushansky A, Ben-Shachar D: Perturbation in mitochondrial network dynamics and in complex I dependent cellular respiration in schizophrenia. Biol Psychiatry 2011, 69: 980–988. doi: 10.1016/j.biopsych.2011.01.010.
- Ai-Ghoul WM, Kim MS, Fazal N, Azim AC, Ali A: Evidence for simvastatin anti-inflammatory actions based on quantitative analyses of NETosis and other inflammation/oxidation markers. Results Immunol 2014; 4: 14–22. doi: 10.1016/j.rinim.2014.03.001.
- Yun Y, Hou L, Sang N: SO(2) inhalation modulates the expression of pro-inflammatory and pro-apoptotic genes in rat heart and lung. J Hazard Mater 2011; 185: 482–488. doi: 10.1016/j.jhazmat.2010.09.057.
- Khan ME, Gupta GSD: Cellular and biochemical indices of bronchoalveolar lavage for detection of lung injury following insult by airborne toxicants. Toxicol Lett 1991; 58: 239–255.
- Michael S, Montag M, Dott W: Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter. Environ Pollut 2013; 183: 19–29. doi: 10.1016/j.envpol.2013.01.026.
- Chang MY, Tanino Y, Vidova V et al.: Reprint of: a rapid increase in macrophage-derived versican and hyaluronan in infectious lung disease. Matrix Biol 2014; 35: 162–173. doi: 10.1016/j.matbio.2014.04.003.
- Oakley RH, Cidlowski JA: The biology of the glucocorticoid receptor: new signalung mechanisms in health and disease. J Allergy Clin Immunol 2013; 132: 1033–1044. doi: 10.1016/j.jaci.2013.09.007.
- Skraba ICA, Thompson LO, Potapov EV et al.:Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death. J Surg Res 2005; 123: 118–125. doi: http://dx.doi.Org/10.1016/j.jss.2004.07.245.
- Boots AW, Gerloff K, Bartholomé R et al.: Neutrophils augment LPS-mediated pro-inflammatory signaling in human lung epithelial cells. Biochim Biophys Acta 2012; 1823: 1151–1162. doi: 10.1016/j. bbamcr.2012.04.012.
- Porro C, Di Gioia S, Trotta T et al.: Pro-inflammatory effect of cystic fibrosis sputum microparticles in the murine lung. J Cyst Fibros 2013; 12: 721–728. doi: 10.1016/j.jcf.2013.03.002.
- Redmond D, Chiew YS, van Drunen E, Shaw GM, Chase JG: A minimal algorithm for a minimal recruitment model-model estimation of alveoli opening pressure of an acute respiratory distress syndrome (ARDS) lung. Biomed Signal Process Control 2014; 14: 1–8. doi: http://dx.doi.org/10.1016/j.bspc.2014.05.006.
- Oliveira MC, Greiffo FR, Rigonato-Oliveira NC et al.: Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extra pulmonary LPS-induced ARDS. J Photochem Photobiol B 2014; 134: 57–63. doi: 10.1016/j.jphotobiol.2014.03.021.
- Basavaraja GV, Bharath Kumar Reddy KR: Acute respiratory distress syndrome (ARDS) in children with Rickettsial infection — a timely diagnosis saving lives. Pediatr Infect Dis 2013; 5: 119–121. doi: http://dx.doi.org/10.1016/j.pid.2013.03.005.
- Raina AH, Bhat A, Bhat FA et al.: Pulmonary tuberculosis presenting with acute respiratory distress syndrome (ARDS): a case report and review of literature. Egypt J Chest Dis Tuberc 2013; 62: 655–659.
- Thompson BT, Bernard GR: ARDS Network (NHLBI) studies: successes and challenges in ARDS clinical research. Crit Care Clin 2011; 27: 459–468. doi: 10.1016/j.ccc.2011.05.011.
- Go S-I, Lee A, Lee US et al.: Clinical significance of the neutrophil-lymphocyte ratio in venous thromboembolism patients with lung cancer. Lung Cancer 2014; 84: 79–85. doi: 10.1016/j.lungcan.2014.01.014.
- Guyot N, Wartelle J, Malleret L et al.: Unopposed cathepsin g, neutrophil elastase, and proteinase 3 cause severe lung damage and emphysema. Am J Pathol 2014; 184: 2197–2210. doi: 10.1016/j.ajpath.2014.04.015.
- Yoshida T, Nagai K, Inomata T, Ito Y, Betsuyaku T, Nishimura M: Relationship between neutrophil influx and oxidative stress in alveolar space in lipopolysaccharide-induced lung injury. Respir Physiol Neurobiol 2014; 191: 75–83. doi: 10.1016/j.resp.2013.11.008.
- Sakashita A, Nishimura Y, Nishiuma T et al.: Neutrophil elastase inhibitor (sivelestat) attenuates subsequent ventilator-induced lung injury in mice. Eur J Pharmacol 2007; 571: 62–71. doi:10.1016/j.ejphar.2007.05.053.
- Paumann-Page M, Furtmüller PG, Hofbauer S, Paton LN, Obinger C, Kettle AJ: Inactivation of human myeloperoxidase by hydrogen peroxide. Arch Biochem Biophys 2013; 539: 51–62. doi: 10.1016/j.abb.2013.09.004.
- Oliveira VR, Carvalho GMC, Avila MB et al.: Time-dependence of lung injury in mice acutely exposed to cylindrospermopsin. Toxicon 2012; 60: 764–772. doi: 10.1016/j.toxicon.2012.06.009.
- Asha Devi S, Manjula KR: Intermittent cold-induced hippocampal oxidative stress is associated with changes in the plasma lipid composition and is modifiable by vitamins C and E in old rats. Neurochem Int 2014; 74: 46–52. doi: 10.1016/j.neuint.2014.05.001.
- Turk R, Podpeĉan O, Mrkun J et al.: Lipid mobilisation and oxidative stress as metabolic adaptation processes in dairy heifers during transition period. Anim Reprod Sci 2013; 141 :109–115. doi: 10.1016/j.anireprosci.2013.07.014.
- Comar JF, Babeto de Sá-Nakanishi A, de Oliveira AL et al.: Oxidative state of the liver of rats with adjuvant-induced arthritis. Free Radic Biol Med 2013; 58: 144–153. doi: 10.1016/j.freeradbiomed.2012.12.003.
- Lanzetti M, da Costa CA, Nesi RT et al.: Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema. Free Radic Biol Med 2012; 53: 1993–2001. doi: 10.1016/j.freeradbiomed.2012.09.015.
- Güler H, Ata F: Design and implementation of training mechanical ventilator set for clinicians and students. Procedia — Soc Behav Sci 2013; 83: 493–496. doi: 10.1016/j.sbspro.2013.06.095.
- Yan L-J: Positive oxidative stress in aging and aging-related disease tolerance. Redox Biol 2014; 2: 165–169. doi: 10.1016/j.redox.2014.01.002.
- Teclebrhan H, Jakobsson-Borin A, Brunk U, Dallner G: Relationship between the endoplasmic reticulum-Golgi membrane system and ubiquinone biosynthesis. Biochim Biophys Acta — Lipids Lipid Metab 1995; 1256: 157–165.
- Kozlov AV, Bahrami S, Calzia E et al.: Mitochondrial dysfunction and biogenesis: do ICU patients diefrom mitochondrial failure? Ann Intensive Care 2011; 1: 41. doi: 10.1186/2110-5820-1-41.
- Burkhardt M, Nienaber U, Pizanis A et al.: Acute management and outcome of multiple trauma patients with pelvic disruptions. Crit Care 2012; 16: R163. doi: 10.1186/cc11487.
- Hybertson BM, Gao B, Bose SK, McCord JM: Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med 2011; 32: 234–246. doi: 10.1016/j.mam.2011.10.006.
- Ciesla DJ, Moore EE, Johnson JL et al.: Decreased progression of postinjury lung dysfunction to the acute respiratory distress syndrome and multiple organ failure. Surgery 2006; 140: 640–647. doi: http://dx.doi.org/10.1016/j.surg.2006.06.015.
- Yang Q, Liu X, Liu M, Zhang L, Guan Y: Ulinastatin-mediated protection against zymosan-induced multiple organ dysfunction in rats. Biologicals 2010; 38: 552–556. doi: 10.1016/j.biologicals.2010.05.001.
- Blasiole B, Bayr H, Vagni VA et al: Effect of hyperoxia on resuscitation of experimental combined traumatic brain injury and hemorrhagic shock in mice. Anesthesiology 2013; 118: 649–663. doi: 10.1097/ALN.0b013e318280a42d.
- Lee C-C, Chang l-J, Yen Z-S et al: Delayed fluid resuscitation in hemorrhagic shock induces proinflammatory cytokine response. Ann Emerg Med 2007; 49: 37–44. doi: http://dx.doi.Org/10.1016/j.annemergmed.2006.05.031.
- Devlin JJ, DeVito SS, Littlejohn LF et al.: Terlipressin with limited fluid resuscitation in a swine model of hemorrhage. J Emerg Med 2013; 45: 78–85. doi: 10.1016/j.jemermed.2012.12.023.
- Lavhale MS, Davalad S, Gulati A: Resuscitative effect of centhaquin after hemorrhagic shock in rats. J Surg Res 2013; 179: 115–124. doi: 10.1016/j.jss.2012.08.042.
- Morrison JJ, Ross JD, Markov NP, Scott DJ, Spencer JR, Rasmussen TE:The inflammatory sequelae of aortic balloon occlusion in hemorrhagic shock. J Surg Res 2014; 186: 1–9. doi: 10.1016/j.jss.2014.04.012.
- Hwabejire JO, Lu J, Liu B, Li Y, Halaweish I, Alam HR: Valproic acid for the treatment of hemorrhagic shock: a dose-optimization study. J Surg Res 2014; 186: 363–370. doi: 10.1016/j.jss.2013.09.016.
- Saad KR, Saad PF, Dantas Filho L et al.: Pulmonary impact of N-acetylcysteine in a controlled hemorrhagic shock model in rats. J Surg Res 2013; 182: 108–115. doi: 10.1016/j.jss.2012.07.037.
- Sun Y-X, Wu X-S, Gao Z, Wang F, Liu S, Chen X-L: Effect of 200 mEq/L Na+ hypertonic saline resuscitation on systemic inflammatory response and oxidative stress in severely burned rats. J Surg Res 2013; 185: 477–484. doi: 10.1016/j.jss.2013.06.039.
- Finfer S: Clinical controversies in the management of critically ill patients with severe sepsis: resuscitation fluids and glucose control. Virulence 2014; 5: 200–205. doi: 10.4161/viru.25855.
- Wu J, Meeker JG, Chiamvimonvat N: Antioxidant enzyme gene transfer for ischemic diseases. Adv Drug Deliv Rev 2009; 61: 351–363. doi: 10.1016/j.addr.2009.01.005.
- Öztürk M, Kolak U, Τοpçu G, Öksüz S, Choudhary Ml: Antioxidant and anticholinesterase active constituents from Micromeria cilicica by radical-scavenging activity-guided fractionation. Food Chem 2011; 126: 31–38. doi: 10.1016/j.foodchem.2010.10.050.
- Harrison FE, Meredith ME, Dawes SM, Saskowski JL, May JM: Low ascorbic acid and increased oxidative stress in gulo (–/–) mice during development. Brain Res 2010; 1349: 143–152. doi: 10.1016/j.brainres.2010.06.037.
- Rajendran P, Nandakumar N, Rengarajan T et al.: Antioxidants and human diseases. Clin Chim Acta 2014; 436C: 332–347. doi: 10.1016/j.cca.2014.06.004.
- Xiao Y, Xing G, Rui X et al.: Enhancement of the antioxidant capacity of chickpeas by solid state fermentation with Cordyceps militaris SN-18. J Funct Foods 2014; 10: 210–222. doi: http://dx.doi.Org/10.1016/j. jff.2014.06.008.
- Hong J, Chen T-T, Hu P, Yang J, Wang S-Y: Purification and characterization of an antioxidant peptide (GSQ) from Chinese leek (Allium tuberosum Rottler) seeds. J Funct Foods 2014; 10: 144–153. doi:10.1016/j. jff.2014.05.014.
- Harakotr B, Suriharn B, Tangwongchai R, Scott MP, Lertrat K: Anthocyanin, phenolics and antioxidant activity changes in purple waxy corn as affected by traditional cooking. Food Chem 2014; 164: 510–517. doi: 10.1016/j.foodchem.2014.05.069.
- Chuang C-C, Shiesh S-C, Chi C-H et al.: Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis. Crit Care 2006; 10: R36. doi:10.1186/cc4826.
- Blass SC, Goost H, Tolba RH et al.: Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrientsand glutamine: a PRCT. Clin Nutr 2012; 31: 469–475. doi: 10.1016/j.clnu.2012.01.002.
- Arent AM, Souza LF De, Walz R, Dafre AL: Perspectives on Molecular Biomarkers of Oxidative Stress and Antioxidant Strategies in Traumatic Brain Injury. Bio Med Res Int 2013; 2014. doi: 10.1155/2014/723060.
- Obeid R, Herrmann W: Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 2006; 580: 2994–3005. doi: http://dx.doi.Org/10.1016/j.febslet.2006.04.088.
- Ribeiro A, Ferraz-de-Paula V, Pinheiro ML et al.: Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a muine model of acute lung injury: role for the adenosine A(2A) receptor. Eur J Pharmacol 2012; 678: 78–85. doi: 10.1016/j.ejphar.2011.12.043.
- Benetti LR, Campos D, Gurgueira S et al.: Hydrogen sulfide inhibits oxidative stress in lungs from allergic mice in vivo. Eur J Pharmacol 2013; 698: 463–469. doi: 10.1016/j.ejphar.2012.11.025.
- Wu F-J, Xue Y, Liu X-F et al.: The protective effect of eicosapentaenoic acid-enriched phospholipids from sea cucumber Cucumaria frondosa on oxidative stress in PC12 cells and SAMP8 mice. Neurochem Int 2014; 64: 9–17. doi: 10.1016/j.neuint.2013.10.015.
- Santos RS, Silva PL, Oliveira GP et al.: Effects of oleanolic acid on pulmonary morphofunctional and biochemical variables in experimental acute lung injury. Respir Physiol Neurobiol 2011; 179: 129–136. doi: 10.1016/j.resp.2011.07.008.
- Joo Choi R, Cheng M-S, ShikKim Y: Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury. Redox Biol 2014; 2: 504–512. doi: 10.1016/j.redox.2014.02.001.
- Torres RL, Lucena I, Laste G et al.: Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs. J Bras Pneumol 2014; 40: 238–243. doi: http://dx.doi.org/10.1590/S180637132014000300006.
- Kutsukake M, Matsutani T, Tamura K et al.: Pioglitazone attenuates lung injury by modulating adipose inflammation. J Surg Res 2014; 189: 295–303. doi: 10.1016/j.jss.2014.03.007.
- Straaten HMO, Spoelstra-de Man AME, de Waard MC: Vitamic C revisited. Crit Care 2014; 18: 460. doi: 10.1186/s13054-014-0460-x.
- Wischmeyer PE, Dhaliwal R, McCall M, Ziegler TR, Heyland DK: Parenteral glutamine supplementation in critical illness: a systematic review. Crit Care 2014; 18: R76. doi: 10.1186/cc13836.
- Ayvaz S, Aksu B, Karaca T et al.: Effects of methylene blue in acute lung injury induced by blunt chest trauma. Hippokratia 2014; 18: 50–56.
- Qin Z-S, Tian P, Wu X, Yu H-M, Guo N: Effects of ulinastatin administered at different time points on the pathological morphologies of the lung tissues of rats with hyperthermia. ExpTher Med 2014; 7:1625–1630. doi: 10.3892/etm.2014.1656.
- Liu M-W, Su M-X, Qin L-F et al.: Effect of salidrosideon lung injury by upregulating peroxisome proliferator-activated receptor γ expression in septic rats. Exp Ther Med 2014; 7: 1446–1456. doi: 10.3892/etm.2014.1629.
- Kale V, Freysdottir J, Paulsen BS, Friðjónsson ÓH, Óli Hreggviðsson G,
Omarsdottir S: Sulphated polysaccharide from the sea cucumber Cucumaria frondosa affect maturation of human dendritic cells and their activation of allogeneic CD4(+) T cells in vitro. Bioact Carbohydrates Diet Fibre 2013; 2: 108–117.
- La M-P, Shao J-J, Jiao J, Yi Y-H: Three cerebrosides from the sea cucumber Cucumaria frondosa. Chin J Nat Med 2012; 10: 105–109. doi: 10.3724/SP.J.1009.2012.00105.
- Webber V, Dutra SV, Spinelli FR, Marcon ÄR, Carnieli GJ, Vanderlinde R: Effect of glutathione addition in sparkling wine. Food Chem 2014; 159: 391–398. doi: 10.1016/j.foodchem.2014.03.031.
- Petronilho F, Perico SR, Vuolo F et al.: Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment. Brain Behav Immun 2012; 26: 904–910. doi: 10.1016/j.bbi.2012.03.007.
- Melo AC, Valença SS, Gitirana LB et al.:Redox markers and inflammation are differentially affected by atorvastatin, pravastatin or simvastatin administered before endotoxin-induced acute lung injury. Int Immunopharmacol 2013; 17: 57–64. doi: 10.1016/j.intimp.2013.05.016.
- Bernabé García J, Zafrilla Rentero P, Mulero Cánovas J, Gómez Jara P, Leal Hernández M, Abellán Alemán J: Biochemical and nutritional markers and antioxidant activity in metabolic syndrome. Endocrinol Nutr 2014; 61: 302–308. doi: 10.1016/j.endonu.2014.01.006.
- Cavaillon J-M: Controversies surrounding current therapies for sepsis syndrome. Bull Inst Pasteur 1995; 93: 21–41.
- Romieu I, Castro-Giner F, Kunzli N, Sunyer J: Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J 2008; 31: 179–197. doi: 10.1183/09031936.00128106.
- Wu J, Wei J, You X et al.: Inhibition of hydrogen sulfide generation contributes to lung injury after experimental orthotopic lung transplantation. J Surg Res 2013; 182: e25–33. doi: 10.1016/j.jss.2012.09.028.
- Verkhovskaya M, Wikström M: Oxidoreduction properties of bound ubiquinone in Complex I from Escherichia coli. Biochim Biophys Acta 2014; 1837: 246–250. doi: 10.1016/j.bbabio.2013.11.001.
- López Fontana CM, Pérez-Elizalde RF, Vanrell MCM, Recalde GM, Uvilla AL, López-Laur JD: Relation between selenium plasma levels and different prostatic pathologies. Actas Urológicas Españolas 2010; 34: 625–629. doi: 10.1016/S2173-5786(10)70151-7.
- Bezerra FJL, Bezerra do Vale N, Macedo B de O, Rezende AA, Almeida M das G: Evaluation of antioxidant parameters in rats treated with sevoflurane. Brazilian J Anesthesiol 2010; 60: 162–169. doi: http://dx.doi.org/10.1590/S0034-70942010000200008.
- Nelson EJ, MacDonald BA, Robinson SMC: The absorption efficiency of the suspension-feeding sea cucumber, Cucumaria frondosa, and its potential as an extractive integrated multi-trophic aquaculture (IMTA) species. Aquaculture 2012; 370–371: 19–25. doi:10.1016/j.aquaculture.2012.09.029.
- Das UN: n-3 fatty acids, gama-linolenic acid, and antioxidants in sepis. Crit Care 2013; 17: 312. doi: 10.1186/cc12574.
- George TJ, Arnaoutakis GJ, Beaty CA et al.: Hydrogen sulfide decreases reactive oxygen in a model of lung transplantation. J Surg Res 2012; 178; 494–501. doi: 10.1016/j.jss.2012.02.065.
- George TJ, Arnaoutakis GJ, Beaty CA et al.: Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation. J Surg Res 2012; 178: 593–600. doi: 10.1016/j.jss.2012.06.037.
- Sunil VR, Vayas KN, Cervelli JA et al.: Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. Exp Mol Pathol 2014; 97: 89–98. doi: 10.1016/j.yexmp.2014.05.009.
- Xu L, Li Y, Wan S, Wang Y, Yu P: Protective effects of apocynin nitrone on acute lung injury induced by lipopolysaccharide in rats. Int Immunopharmacol 2014; 20: 377–382. doi: 10.1016/j.intimp.2014.03.014.
- Chen Y, Wu H, Nie Y-C, Li P-B, Shen J-G, Su W-W: Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs. Environ Toxicol Pharmacol 2014; 38: 279–287. doi: 10.1016/j.etap.2014.04.030.
- Kovacs E, Xu L, Pasek DA, Liliom K, Meissner G: Regulation of ryanodine receptors by sphingosylphosphorylcholine: Involvement of both calmodulin-dependent and independent mechanisms. Biochem Biophys Res Commun 2010; 401: 281–286. doi: 10.1016/j.bbrc.2010.09.050.
- Su Z-Q, Mo Z-Z, Liao J-B et al.: Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress. Int Immunopharmacol 2014; 22: 371–378. doi: 10.1016/j.intimp.2014.06.043.
- Türüt H, Kurutas EB, Bulbuloglu E, Yasim A, Ozkaya M, Onder A et al.: Zinc aspartate alleviates lung injury induced by intestinal ischemia-reperfusion in rats. J Surg Res 2009; 151: 62–67. doi: 10.1016/j.jss.2008.01.004.
- Avian D, Taşkinlar H, Tamer L et al.: Protective effect of trapidil against oxidative organ damage in burn injury. Burns 2005; 31: 859–865. doi: http://dx.doi.Org/10.1016/j.burns.2005.04.013.
- Macit E, Yaren H, Aydin I et al.: The protective effect of melatonin and S-methylisothiourea treatments in nitrogen mustard induced lung toxicity in rats. Environ Toxicol Pharmacol 2013; 36: 1283–1290. doi: 10.1016/j.etap.2013.10.001.
Alexandru Florin Rogobete, Chemist
Clinic of Anaesthesia and Intensive Care,
Emergency County Hospital, Timisoara, Romania
Bd. Iosif Bulbuca nr. 10
e-mail: firstname.lastname@example.org, email@example.com