The effects of chloramphenicol, thiamphenicol and florfenicol on glucose 6-phosphate dehydrogenase (G6PD), reduced glutathione (GSH) enzyme activities and some haematological parameters in mice

Bu çalışmanın amacı farelerde, eritrositlerin serbest radikal metabolizmasında rol oynayan glukoz-6 fosfat dehidrogenaz (G6PD) ve glutatyon (GSH) enzim aktiviteleri ile kan değerleri üzerine kloramfenikol, tiamfenikol ve florfenikolün etkilerinin araştırılmasıdır. Çalışmada 70 adet Swiss albino erkek fare kullanıldı. Hayvanlar herbirinde 10 adet fare olacak şekilde 7 gruba ayrıldı. Her bir antibiyotik içme suları ile ad libitum olarak 0 (kontrol), 100 mg/kg ve 200 mg/kg dozlarında 7 gün uygulandı. Biyokimyasal ve hematolojik analizler uygulamanın 1. ve 7. günleri ile takip eden 14. günde yapıldı. Kloramfenikol ve tiamfenikolün her iki dozu GSH ve G6PD enzim aktivitelerini kontrol grubuna oranla 7. ve 14. günlerde istatistiksel olarak önemli oranda düşürürken (p < 0.05) florfenikolün etki yapmadığı tespit edildi. Bununla birlikte tiamfenikolün sadece yüksek dozu ve kloramfenikolün ise her iki dozu kontrol grubu ile karşılaştırıldığında 14. günde alyuvar sayısı (RBC), hemoglobin (Hb) düzeyi, hematokrit (PCV) değer, akyuvar sayısı (WBC) ve nötrofil yüzde oranını önemli oranda azalttı(p < 0.05). Elde edilen bulgular farelerde kloramfenikol ve tiamfenikolün eritrosit GSH ve G6PD enzim aktivitesi ile bazı hematolojik parametreler üzerine engelleyici bir etkiye sahip olduğunu gösterdi.

Farelerde glukoz-6 fosfat dehidrogenaz (G6PD), redükte glutatyon (GSH) enzim aktiviteleri ile bazı hematolojik parametreler üzerine kloramfenikol, tiamfenikol ve florfenikolün etkileri.

The aim of present study was to investigate the effects of chloramphenicol thiamphenicol and florfenicol on activities of reduced glutathione (GSH) and glucose-6 phosphate dehydrogenase (G6PD) enzymes that play an important role in the free radical metabolism of erythrocytes and haematological parameters in the mice. In the study, 70 male Swiss albino mice were used. Animals were divided into seven groups, each having 10 mice. Each antibiotic were given ad libitum in drinking water at levels of 0 (control), 100 mg/kg and 200 mg/kg for 7 days. Biochemical and haematological analysis were studied on days 1, 7 and following 14. Both dosages of chloramphenicol and thiamphenicol, but not florfenicol were induced a significant reduction (p < 0.05) in GSH and G6PD enzyme activities on days 7 and 14 compared to control group. Hovewer, only high dosage of thiamphenicol and both dosage of chloramphenicol were induced a significant (p < 0.05) decrease in red blood cell (RBC) count, hemoglobin (Hb) value, packed cell volume (PCV) , white blood cell (WBC) and neutrophil percentage on day 14 compared to control group. The present findings indicate that chloramphenicol and thiamphenicol have significant inhibition effects on the activities of erythrocytes GSH, G6PD enzymes and some haematological parameters in mice.

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Ando, J., Ishihora, R., Imai, S., Takano, S., Kitamura, T., Takahashi, M., Yoshida, M., Maekawa, A., 1997 Thirteen week subchronic toxicity study of thiamphenicol in F344 rats. Toxicol Let., 91, 137–146.
Andrews, MM., Mooney, KH., 1994 Alterations in hematologic function in children. In: McCance KL, Huether SE, Eds. Pathophysiology, The end biologic basis for disease in adults, and children. 2 ed. USA: Mosby-Year Book Inc., 908–942.
Barhoumi, R., Hartford, B., Robert, C., 1995 Kinetic analysis of glutathione in anchored cells with monochlorobimane. Cytometry, 19, 226–234.
Beydemir, S., Ciftci, M., Ozmen, I., Buyukokuroglu, ME., Ozdemir, H., Kufrevioglu, OI., 2000 Effects of some medical drugs on enzyme activity of carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo. Pharmacol Res., 42, 187–191.
Beutler, E., 1971 Red cell metabolism. In: Manuel of biochemical methods. London: Academic Press.
Chaudiere, J., Aguini, N., Yadan, J., 1999 Nonenzymic colorimetric assay of glutathione in the presence of other mercaptans. Meth Enzymol., 299, 276–286.
Christensen, GM., Olson, D., Riedel B., 1982 Chemical effects on the activity of eight enzymes: a review and a discussion relevant to environmental monitoring. Environ Res, 29, 247-255.
Ciftci, M., Kufrevioglu, OI., Gundogdu, M., Ozmen, I., 2000 Effects of some antibiotics on enzyme activity of glucose-6-phosphate dehydrogenase from human erythrocytes. Pharm Res., 41, 109–113.
Ciftci, M., Ozmen, I., Buyukokuroglu, ME., Pence, S., Kufrevioglu, OI., 2001 Effects of metamizol and magnesium sulfate on enzyme activity of glucose-6 phosphate dehydrogenase from human erthrocytes in vitro and rat erythrocytes in vivo. Clin Biochem., 34, 297–302.
Ciftci, M., Beydemir, S., Yilmaz, H., Bakan, E., 2002 Effects of some drugs on rat erythrocyte 6- phosphogluconate dehydrogenase: an in vitro and in vivo study. Pol J Pharmacol., 54, 275–280.
De Renzo, A., Formisano, S., Rotoli, B., 1981 Bone marrow aplasia and thiamphenicol. Haematology, 66, 98–104.
Erdogan, O., Ciftci, M., Ciltas, A., Hisar, O., 2004 Inhibition effects of some antibiotics on th activity of glucose 6- phosphate dehydrogenase enzyme from Rainbow Trout (Oncorhynchus mykiss Walbaum, 1792) erythrocytes. Turk J Vet Anim Sci., 28, 675–681.
Ferrari, V., Pajola, E., 1981 Types of haemopoietic inhibition by chloramphenicol and thiamphenicol. In: Najean, Y, Tognoni, G, Yunis, A.A. (Eds.), Safety Problems Related to Chloramphenicol and Thiamphenicol. Raven Press, New York, 43–59.
Holt, DE., Andrews, CM., Payne, JP., Williams, TC., Turton, JA., 1998 The myelotoxicity of chloramphenicol: in vitro and in vivo studies: II: in vivo myelotoxicity in the B6C3F1 mouse. Hum Exp Tox., 17, 8–17.
Keiser, G., 1974 Cooperative study of patients treated with thiamphenicol. Comparative study of patients treated with chloramphenicol and thiamphenicol. Postgrad Med J., 50, 143–145.
Krako, IH., Karnofsky, DA., Burchenal, JH., 1955 Effects of large doses of chloramphenicol on human subjects. New Eng J Med., 253, 7–10.
Lehninger, AL., Nelson, DL., Cox, MM., 2000 Principles of Biochemistry. 3rd edit: CBS publishers, New Delhi.
Manyan, DR., Arimura, GK., Yunis, AA., 1972 Chloramphenicol induced erythroid supression and bone marrow ferrochelatase activity in dogs. J Lab Clin Med., 79, 137–144.
Manyan, DR., Yunis, AA., 1970 The effect of chloramphenicol treatment on ferrochelatase activity in dogs. Biochem Biophys Res Commun., 41, 926–931.
Mitruka, BM., Rawnsley, HM., 1977 Clinical, biochemical and hematological reference values in normal experimental animals. Masson Publishing, New York, USA.
Neu, HC., Fu, KP., 1980 In vitro activity of chloramphenicol and thiamphenicol analogs. Antimicrob Agents Ch, 18, 311–316.
Nijhof, W., Kroon, AM., 1974 The interference of chloramphenicol and thiamphenicol with the biogenesis of mitochondria in animal tissues: a possible clue to the toxic action. Postgrad Med J, 50, 53–59.
Prescott, JF., Baggot, JD., 1993 Chloramphenicol, thiamphenicol and florfenicol, In J. F. Prescott, and J. D. Baggot (ed.), Antimicrobial therapy in veterinary medicine, 2nd ed. Iowa State University Press, Iowa City, Iowa. 205–214.
Sams, RA., 1994 Florfenicol: chemistry and metabolism of a novel broadspectrum antibiotic. In: Proceedings of the XVIII World Buiatrics Congress. Bologna, Italy. 13–17.
Sams, RA., 1995 Chemistry and metabolism of a novel-broad-spectrum antibiotic. Tieraerztl Umschau., 50, 703–707.
Schaeffer, F., Stainer, RY., 1978 Glucose-6-phosphate Dehydrogenase. Kinetics and Molecular Properties. Arch Microbiol., 116,8.
Skolimowski, IM., Knight, RC., Edwards, DI., 1983 Molecular basis of chloramphenicol and thiamphenicol toxicity to DNA in vitro. J Antimicrob Chemother, 12, 535–42.
Srivastava, SK., Beutler, E., 1989 Glutathione metabolism of erythrocyte. The enzymatic cleavage of glutathione-haemoglobine preperations by glutathione reductase. Biochem J., 119, 353.
Takamizawa, I., 1984 The effects of chloramphenicol and thiamphenicol on the peripheral blood and bone marrow of normal rabbits. J Tokyo Med Coll., 42, 741–753.
Telefoncu, A., Telefoncu, F., 1989 Glukoz-6-fosfat dehidrogenaz aktivitesine primaquine’nin etkisi. Turk J Med Sci., 14,57–63.
Tomoeda, M., Yamamoto, K., 1981 The hematologic adverse reaction experience with thiamphenicol in Japan. In: Y. Najean et al. (Eds.), Safety Problems Related to Chloramphenicol and Thiamphenicol Therapy, Raven Press, New York, USA. 103–l10.
Turton, JA., Yallop, D., Andrews, M., Fagg, R., York, M., Williams, TC., 1999 Haemotoxicity of chloramphenicol succinate in the CD-1 mouse and Wistar Hanover rat. Hum Exp Tox, 18, 566–576.
Ueda, Y., Suenag, AI., 1995 In vitro antibacterial activity of florfenicol against Actinobacillus pleuropneumonia. J Vet Med Sci., 57, 364–365.
Yunis, AA., 1988 Chloramphenicol: relation of structure to activity and toxicity. Annu Rev Pharmacol Toxicol., 28, 83–100.
Yuregir, GT., Aksoy, K., Arpaci, A., Unlukurt, I., Tuli, A., 1994 Studies on red cell glucose-6-phosphate dehydrogenase, evaluation of reference values. Ann Clin Biochem., 31,50.