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The effects of amifostine and dexamethasone on brain tissue lipid peroxidation during oxygen treatment of carbon monoxide-poisoned rats

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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

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. Gorman D, Drewry A, Huang YL, Sames C. The clinical toxicology of carbon monoxide.Toxicology. 2003; 187: 25–38.

    Article  PubMed  CAS  Google Scholar 

  3. Warner DS, Sheng H, Haberle IB. Oxidants, antioxidants and the ischemic brain.J Exp Biol. 2004; 207: 3221–3231.

    Article  PubMed  CAS  Google Scholar 

  4. Cobb JP, Hotchkiss RS, Karl E, Buchman TG. Mechanisms of cell injury and death.Br J Anaesth. 1996; 77: 3–10.

    PubMed  CAS  Google Scholar 

  5. Omaye ST. Metabolic modulation of carbon monoxide toxicity.Toxicology. 2002; 180: 139–150.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    PubMed  CAS  Google Scholar 

  11. Piantadosi CA. Carbon monoxide poisoning.N Engl J Med. 2002; 347: 1054–1055.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Thom SR. Antagonism of carbon monoxide mediated brain lipid peroxidation by hyperbaric oxygen.Toxicol Appl Pharmacol. 1990; 105: 340–344.

    Article  PubMed  CAS  Google Scholar 

  14. Thom SR. Hyperbaric-oxygen therapy for acute carbon monoxide poisoning.N Engl J Med. 2002; 347: 1105–1106.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. Spencer CM, Goa KL. Amifostine.Drugs. 1995; 50: 1001–1025.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. Tietz NW, Fiereck EA. The spectrophotometric measurement of carboxyhemoglobin.Ann Clin Lab Sci. 1973; 3: 36–42.

    PubMed  CAS  Google Scholar 

  19. Thom SR. Carbon monoxide-mediated brain lipid peroxidation in the rat.J Appl Physiol. 1990; 68: 997–1003.

    PubMed  CAS  Google Scholar 

  20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem. 1979; 95: 351–358.

    Article  PubMed  CAS  Google Scholar 

  21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 193: 265–275.

    PubMed  CAS  Google Scholar 

  22. Sun Y, Oberly LW, Li Y. A simple method for clinical assay of super oxide dismutase.Clin Chem. 1988; 34: 479–500.

    Google Scholar 

  23. Paglia DE, Valentine WN. Studies on the quantitative and the qualitative characterization of erythrocyte glutathione peroxidase.J Lab Clin Med. 1967; 70: 158–169.

    PubMed  CAS  Google Scholar 

  24. Myers RA, Britten JS. Are arterial blood gases of value in treatment decisions for carbon monoxide poisoning?Crit Care Med. 1989; 17: 139–142.

    Article  PubMed  CAS  Google Scholar 

  25. Santini V. Amifostine: chemotherapeutic and radio therapeutic protective effects.Expert Opin Pharmacother. 2001; 2: 479–489

    Article  PubMed  CAS  Google Scholar 

  26. 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.

    Article  PubMed  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

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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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