Abstract
The mechanisms of injury of, and methods of treating patients with, carbon monoxide (CO) poisoning are poorly understood. Besides the hypoxic degenerative effects of CO, reoxygenation injury may play an important role. Amifostine (Ami), which is most often used in radiotherapy for its tissue protective characteristics, may offer benefits. In this study, investigators evaluated the effectiveness of various treatments in a CO-poisoned rat model. A total of 36 Wistar rats were randomly assigned to 1 of 6 groups (n=6 each), including control and poisoned groups exposed to CO at 2000 ppm (v/v) for 1 h, followed by various 1-h treatments: group C (control), group CO-air (ambient air), group CO-NBO (normobaric 100% oxygen), group CO-HBO (hyperbaric oxygen with 3 atmospheres absolute [3 ATA]), group CO-NBO-Ami (normobaric oxygen with intraperitoneal [IP] injection of amifostine 250 mg/kg body weight [bw]), and group CO-70O (70% O2 and 5% CO2 with dexamethasone 10 mg/kg bw, IP). Blood gas analysis, carboxy-hemoglobin determination, brain tissue lipid peroxidation, and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and creatine kinase (CK) activities were evaluated. Carboxyhemoglobin concentration in the air-treated group was 44±2%; it decreased to the control level with all oxygen treatments. Brain tissue GSH-Px and SOD measurements did not change. The activity of LDH in group CO-HBO and the activities of LDH and CKin group CO-70O were similar to those of group C. Lipid peroxides were high in ambient air and normobaric oxygen, but HBO, amifostine with oxygen, or 70% O2 reduced these to control levels (P < .05).
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References
Miro O, Alonso JR, Casademont J, Jarreta D, Urbano-Marquez A, Cardellach F. Oxidative damage on lymphocyte membranes is increased in patients suffering from acute carbon monoxide poisoning.Toxicol Lett. 1999; 110: 219–223.
Gorman D, Drewry A, Huang YL, Sames C. The clinical toxicology of carbon monoxide.Toxicology. 2003; 187: 25–38.
Warner DS, Sheng H, Haberle IB. Oxidants, antioxidants and the ischemic brain.J Exp Biol. 2004; 207: 3221–3231.
Cobb JP, Hotchkiss RS, Karl E, Buchman TG. Mechanisms of cell injury and death.Br J Anaesth. 1996; 77: 3–10.
Omaye ST. Metabolic modulation of carbon monoxide toxicity.Toxicology. 2002; 180: 139–150.
Thom SR, Bhopale V, Fisher D, Manevich Y, Huang PL, Buerk DG. Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressure of oxygen: an oxidative stress response.J Neurobiol. 2002; 51: 85–100.
Loiseaux-Meunier MN, Bedu M, Gentou C, Pepin D, Coudert J, Caillaud D. Oxygen toxicity: simultaneous measure of pentane and malondialdehyde in humans exposed to hyperoxia.Biomed Pharmacother. 2001; 55: 163–169.
Elayan IM, Axley MJ, Prasad PV, Ahlers ST, Auker CR. Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain.J Neurophysiol. 2000; 83: 2022–2029.
Penney D, Maziarka T. Effect of acute carbon monoxide poisoning on serum lactate dehydrogenase and creatine phosphokinase.J Toxicol Environ Health. 1976; 1: 1017–1021.
Arakawa H, Kodama H, Matsuoka N, Yamaguchi I. Stress increases plasma enzyme activity in rats:differential effects of adrenergic and cholinergic blockades.J Pharmacol Exp Ther. 1997; 280: 1296–1303.
Piantadosi CA. Carbon monoxide poisoning.N Engl J Med. 2002; 347: 1054–1055.
Thom SR. Functional inhibition of leukocyte B2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats.Toxicol Appl Pharmacol. 1993; 123: 248–256.
Thom SR. Antagonism of carbon monoxide mediated brain lipid peroxidation by hyperbaric oxygen.Toxicol Appl Pharmacol. 1990; 105: 340–344.
Thom SR. Hyperbaric-oxygen therapy for acute carbon monoxide poisoning.N Engl J Med. 2002; 347: 1105–1106.
Rocksen D, Lillichook B, Larsson R, Johansson T, Bucht A. Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation.Clin Exp Immunol. 2000; 122: 249–256.
Spencer CM, Goa KL. Amifostine.Drugs. 1995; 50: 1001–1025.
Facorro G, Sarrasague MM, Torti H, et al. Oxidative study of patients with total body irradiation: effects of amifostine treatment.Bone Marrow Transplant. 2004; 33: 793–798.
Tietz NW, Fiereck EA. The spectrophotometric measurement of carboxyhemoglobin.Ann Clin Lab Sci. 1973; 3: 36–42.
Thom SR. Carbon monoxide-mediated brain lipid peroxidation in the rat.J Appl Physiol. 1990; 68: 997–1003.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem. 1979; 95: 351–358.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 193: 265–275.
Sun Y, Oberly LW, Li Y. A simple method for clinical assay of super oxide dismutase.Clin Chem. 1988; 34: 479–500.
Paglia DE, Valentine WN. Studies on the quantitative and the qualitative characterization of erythrocyte glutathione peroxidase.J Lab Clin Med. 1967; 70: 158–169.
Myers RA, Britten JS. Are arterial blood gases of value in treatment decisions for carbon monoxide poisoning?Crit Care Med. 1989; 17: 139–142.
Santini V. Amifostine: chemotherapeutic and radio therapeutic protective effects.Expert Opin Pharmacother. 2001; 2: 479–489
Thom SR, Bhopale V, Fisher D, Manevich Y, Huang PL, Buerk DG. Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressure of oxygen: an oxidative stress response.J Neurobiol. 2002; 51: 85–100.
Nita DA, Nita V, Spulber ST, et al. Oxidative damage following cerebral ischemia depends on reperfusion—a biochemical study in rat.J Cell Mol Med. 2001; 5: 163–170.
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Atalay, H., Aybek, H., Koseoglu, M. et al. The effects of amifostine and dexamethasone on brain tissue lipid peroxidation during oxygen treatment of carbon monoxide-poisoned rats. Adv Therapy 23, 332–341 (2006). https://doi.org/10.1007/BF02850138
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DOI: https://doi.org/10.1007/BF02850138