DOI QR코드

DOI QR Code

Effect of Glutathione Administration on Serum Levels of Reactive Oxygen Metabolites in Patients with Paraquat Intoxication: A Pilot Study

  • Kim, Jung-Hoon (Department of Internal Medicine, Soonchunhyang University Medical College) ;
  • Gil, Hyo-Wook (Department of Internal Medicine, Soonchunhyang University Medical College) ;
  • Yang, Jong-Oh (Department of Internal Medicine, Soonchunhyang University Medical College) ;
  • Lee, Eun-Young (Department of Internal Medicine, Soonchunhyang University Medical College) ;
  • Hong, Sae-Yong (Department of Internal Medicine, Soonchunhyang University Medical College)
  • 투고 : 2010.01.14
  • 심사 : 2010.05.28
  • 발행 : 2010.09.01

초록

Background/Aims: Based on preliminary in vitro data from a previous study, we proposed that 50 mg/kg glutathione (GSH) would be adequate for suppressing reactive oxygen species in patients with acute paraquat (PQ) intoxication. Methods: Serum levels of reactive oxygen metabolites (ROM) were measured before and after the administration of 50 mg/kg GSH to each of five patients with acute PQ intoxication. Results: In one patient, extremely high pretreatment ROM levels began to decrease prior to GSH administration. However, in the remaining four cases, ROM levels did not change significantly prior to GSH administration. ROM levels decreased significantly after GSH administration in all cases. In two cases, ROM levels decreased below that observed in the general population; one of these patients died after a cardiac arrest at 3 hours after PQ ingestion, while the other represented the sole survivor of PQ intoxication observed in this study. In the survivor, ROM levels decreased during the first 8 hours of GSH treatment, and finally dropped below the mean ROM level observed in the general population. Conclusions: Treatment with 50 mg/kg GSH significantly suppressed serum ROM levels in PQ-intoxicated patients. However, this dose was not sufficient to suppress ROM levels when the PQ concentration was extremely high.

키워드

참고문헌

  1. Ramiro-Puig E, Castell M. Cocoa: antioxidant and immunomodulator. Br J Nutr 2009;101:931-940. https://doi.org/10.1017/S0007114508169896
  2. Deruelle F, Baron B. Vitamin C: is supplementation necessary for optimal health? J Altern Complement Med 2008;14:1291-1298. https://doi.org/10.1089/acm.2008.0165
  3. Lykkesfeldt J. Malondialdehyde as biomarker of oxidative damage to lipidscaused by smoking. Clin Chim Acta 2007;380: 50-58. https://doi.org/10.1016/j.cca.2007.01.028
  4. Koutsokera A, Papaioannou AI, Malli F, et al. Systemic oxidative stress in patients with pulmonary sarcoidosis. Pulm Pharmacol Ther 2009;22:603-607. https://doi.org/10.1016/j.pupt.2009.09.002
  5. Shimada H, Hirai K, Simamura E, et al. Paraquat toxicity induced by voltage-dependent anion channel 1 acts as an NADH-dependent oxidoreductase. J Biol Chem 2009;284:28642-28649. https://doi.org/10.1074/jbc.M109.033431
  6. Hong SY, Yang JO, Lee EY, Lee ZW. Effects of N-acetyl-L-cysteine and glutathione on antioxidant status of human serum and 3T3 fibroblasts. J Korean Med Sci 2003;18:649-654.
  7. Hong SY, Gil HW, Yang JO, et al. Pharmacokinetics of glutathione and its metabolites in normal subjects. J Korean Med Sci 2005; 20:721-726. https://doi.org/10.3346/jkms.2005.20.5.721
  8. Bus JS, Cagen SZ, Olgaard M, Gibson JE. A mechanism of paraquat toxicity in mice and rats. Toxicol Appl Pharmacol 1976; 35:501-513. https://doi.org/10.1016/0041-008X(76)90073-9
  9. Hagen TM, Brown LA, Jones DP. Protection against paraquatinduced injury by exogenous GSH in pulmonary alveolar type II cells. Biochem Pharmacol 1986;35:4537-4542. https://doi.org/10.1016/0006-2952(86)90776-8
  10. Brown LA, Bai C, Jones DP. Glutathione protection in alveolar type II cells from fetal and neonatal rabbits. Am J Physiol 1992; 262(3 Pt 1):L305-L312.
  11. Levy EJ, Anderson ME, Meister A. Transport of glutathione diethyl ester into human cells. Proc Natl Acad Sci U S A 1993;90: 9171-9175. https://doi.org/10.1073/pnas.90.19.9171
  12. Jurima-Romet M, Barber RF, Demeester J, Shek PN. Distribution studies of liposome-encapsulated glutathione administered to the lung. Int J Pharm 1990;63:227-235. https://doi.org/10.1016/0378-5173(90)90129-R
  13. Smith LJ, Anderson J, Shamsuddin M. Glutathione localization and distribution after intratracheal instillation. Implications for treatment. Am Rev Respir Dis 1992;145:153-159. https://doi.org/10.1164/ajrccm/145.1.153
  14. Reed DJ, Ellis WW, Meck RA. The inhibition of gamma-glutamyl transpeptidase and glutathione metabolism of isolated rat kidney cells by L-(alpha S, 5S)-alpha-amino-3-chloro-4, 5-dihydro-5- isoxazoleacetic acid (AT-125; NSC-163501). Biochem Biophys Res Commun 1980;94:1273-1277. https://doi.org/10.1016/0006-291X(80)90557-4
  15. Rajpert-De Meyts E, Shi M, Chang M, et al. Transfection with gamma-glutamyl transpeptidase enhances recovery from glutathione depletion using extracellular glutathione. Toxicol Appl Pharmacol 1992;114: 56-62. https://doi.org/10.1016/0041-008X(92)90096-B
  16. Gil HW, Seok SJ, Jeong DS, Yang JO, Lee EY, Hong SY. Plasma level of malondialdehyde in the cases of acute paraquat intoxication. Clin Toxicol (Phila) 2010;48:149-152.

피인용 문헌

  1. Redox cycling and increased oxygen utilization contribute to diquat-induced oxidative stress and cytotoxicity in Chinese hamster ovary cells overexpressing NADPH-cytochrome P450 reductase vol.50, pp.7, 2010, https://doi.org/10.1016/j.freeradbiomed.2010.12.035
  2. Serum paraquat concentration detected by spectrophotometry in patients with paraquat poisoning vol.2, pp.3, 2010, https://doi.org/10.5847/wjem.j.1920-8642.2011.03.004
  3. Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 Levels in Patients with Acute Paraquat Intoxication vol.26, pp.4, 2011, https://doi.org/10.3346/jkms.2011.26.4.474
  4. Genetic modification of the association of paraquat and Parkinson's disease vol.27, pp.13, 2010, https://doi.org/10.1002/mds.25216
  5. The Time between Paraquat Ingestion and a Negative Dithionite Urine Test in an Independent Risk Factor for Death and Organ Failure in Acute Paraquat Intoxication vol.27, pp.9, 2010, https://doi.org/10.3346/jkms.2012.27.9.993
  6. Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats vol.34, pp.10, 2013, https://doi.org/10.1038/aps.2013.65
  7. The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity vol.34, pp.2, 2010, https://doi.org/10.1177/0960327114533808
  8. Silymarin attenuates paraquat‐induced lung injury via Nrf2‐mediated pathway in?vivo and in?vitro vol.42, pp.9, 2015, https://doi.org/10.1111/1440-1681.12448
  9. Associations between the phenotype and genotype of MnSOD and catalase in periodontal disease vol.19, pp.1, 2010, https://doi.org/10.1186/s12903-019-0877-3