Turgut TOPAL, Muharrem UÇAR, Ercan GÜÇGELDİ, Hakan YAREN, BÜLENT KURT, Recai OĞUR, Ahmet KORKMAZ

Bir kimyasal savaş ajanının böbrekler üzerindeki akut toksititesinin araştırılması

Özet: Kimyasal Savaş Ajanlarının en önemlilerinden bir tanesi olan sülfür mustard (SM) yaşamsal akut ve kronik toksik etkiler gösterir. Etkilenen en önemli organlar arasında akciğerler, deri, göz ve böbrekler gelmektedir. Bu çalışmada nitrojen mustard (NM) ile oluşturulan böbrek hasarına artmış nitrik oksit (NO) ve peroksinitritlerin aracılık edip etmediği araştırılmıştır. Çalışmada indüklenebilir nitrik oksit sentaz inhibitörü (iNOS) olarak aminoguanidin (AG), peroksinitrit süpürücüsü olaran ebselen kullanılmıştır. NM uygulaması böbreklerdeki oksidan ve antioksidan parametrelerde önemli değişimle birlikte, doku hasarına neden olmuştur. Tedavi ajanları önemli oranda koruma sağlamış ve oksidan parametrelerde gerilemeye eşlik eden doku iyileşmeleri gözlenmiştir. Çalışmanın sonuçları, NM’nin böbreklerde oluşturduğu hasarın önlenmesinde benzer özelliklere sahip ilaçların kullanılabileceğini göstermektedir.

Anahtar Kelimeler:

Modeller, hayvan, Kimyasal savaş ajanları, Mustard gazı, Akut toksisite testleri, Sıçan, Wistar, Böbrek

Investigation of acute toxicity of a chemical warfare agent in kidneys

Abstract: One of the most important chemical warfare agents, sulfur mustard (SM) causes crucial acute and chronic toxic effects. Lung, skin, eye and kidneys are the most affected organs. In this work, it was investigated if increased nitric oxide (NO) and peroxynitrite are involved in nitrogen mustard (NM) induced kidney damage. In this experimen, aminoguanidine (AG) as inducible nitric oxide synthase (iNOS) inhibitor and ebselen as peroxynitrite scavenger were used. NM administration resulted in important oxidant and antioxidant changes as well as tissue damage in kidneys. Therapeutic agents showed significant protection and reduced oxidant parameteres leading to tissue healing was observed. Results of this study suggest that drugs with similar properties can be used to protect kidney damage caused by NM.

Keywords:

Models, Animal, Chemical Warfare Agents, Mustard Gas, Acute Toxicity Tests, Rats, Wistar, Kidney,

PDF

___

1. Saladi RN, Smith E, Persaud AN. Mustard: a potential agent of chemical warfare and terrorism. Clin Exp Dermatol 2006; 31 (1):1-5
2. Balali-Mood M, Hefazi M, Mahmoudi M, Jalali E, Attaran D, Maleki M, Razavi ME, Zare G, Tabatabaee A, Jaafari MR. Long-term complications of sulphur mustard poisoning in severely intoxicated Iranian veterans. Fundam Clin Pharmacol 2005; 19 (6):713-21
3. Kehe K, Szinicz. Medical aspects of sulphur mustard poisoning. Toxicology 2005; 214 (2):198-209
4. Balali-Mood M, Hefazi M. The pharmacology, toxicology, and medical treatment of sulphur mustard poisoning. Fundam Clin Pharmacol 2005; 19 (3):297-315
5. Bobb AJ, Arfsten DP, Jederberg WW. N-acetyl-L-Cysteine as prophylaxis against sulfur mustard. Mil Med 2005; 170 (1):52-6
6. Chatterjee D, Mukherjee S, Smith MG, Das SK. Evidence of hair loss after subacute exposure to 2-chloroethyl ethyl sulfide, a mustard analog, and beneficial effects of Nacetyl cysteine. J Biochem Mol Toxicol 2004; 18 (3):150-3
7. Santini V, Giles FJ. The potential of amifostine: from cytoprotectant to therapeutic agent. Haematologica 1999; 84 (11):1035-42
8. Sawyer TW, Lundy PM, Weiss MT. Protective effect of an inhibitor of nitric oxide synthase on sulphur mustard toxicity in vitro. Toxicol Appl Pharmacol 1996; 141 (1):138-44
9. Sawyer TW. Modulation of sulfur mustard toxicity by arginine analogues and related nitric oxide synthase inhibitors in vitro. Toxicol Sci 1998; 46 (1):112-23
10. Sawyer TW, Hancock JR, D'Agostino PA. l-thiocitrulline: A potent protective agent against the toxicity of sulphur mustard in vitro. Toxicol Appl Pharmacol 1998; 151 (2):340-6
11. Yaren H, Mollaoglu H, Kurt B, Korkmaz A, Oter S, Topal T, Karayilanoglu T. Lung toxicity of nitrogen mustard may be mediated by nitric oxide and peroxynitrite in rats. Res Vet Sci 2007; 83 (1):116-122
12. Korkmaz A, Yaren H, Topal T, Oter S. Molecular targets against mustard toxicity: implication of cell surface receptors, peroxynitrite production, and PARP activation. Arch Toxicol 2006; 80 (10):662-70
13. Vijayaraghavan R, Kulkarni A, Pant SC, Kumar P, Rao PV, Gupta N, Gautam A, Ganesan K. Differential toxicity of sulfur mustard administered through percutaneous, subcutaneous, and oral routes. Toxicol Appl Pharmacol 2005; 202 (2):180-8
14. Lowry OH RN, Farr AL, Randall RJ. Protein measurement with the folin-phenol reagent. J Biol Chem 1951; 193 (2):265-275
15. Okhawa H ON, Yagi K. Assay or lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979 (4); 95:351-358
16. Sun Y OL, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988 (5): 34:497-500
17. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70 (1):158-69
18. Miranda KM, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate ande nitrite. Nitric Oxide 2001; 5 (1):62-71
19. Benschop HP, van der Schans GP, Noort D, Fidder A, Mars-Groenendijk RH, de Jong LP. Verification of exposure to sulfur mustard in two casualties of the Iran- Iraq conflict. J Anal Toxicol 1997; 21 (4):249-51
20. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271 (5 Pt 1):C1424-37