Effect of Oral Administration of Chloramphenicol on Hematological Profile of Male Charles Foster Rats

Table of contents

1. Introduction

hloramphenicol (CAP) is a broad spectrum antibiotic, was first quarantined from bacterium Streptomyces venezualae in the year 1947. It was available by the trade name of Chloromycetin by Parke Davis & Co. It was prescribed in mass in 1948 in USA following an outburst of enteric fever. In 1949 it was cleared from Federal Food and Drug, since then it has been used and worked upon extensively being a potent inhibitor of protein synthesis (E. Cundliffe and K. McQuillen, 1967).

Some studies suggest the use of CAP in food. Although, most countries have banned CAP from animal food production, still traces of it have been detected in shrimp and other aquaculture products. According to regulations promulgated in 1980's and 1990's, use of CAP in food was banned and countries have established a zero tolerance policy. In Japan, zero tolerance thresholds for CAP is 50 ppb which in USA is 5 ppb. Meat and offal from treated animals contained CAP and its non -genotoxic metabolites (G. Milhaud, 1993).

Even being a potent antibiotic with a broad range of spectrum, the use of CAP is limited due to its association with aplastic anaemia (AA) (M. L. Rich, et al., 1950) and bone marrow suppression (C. E. Amberkar, et al., 2000). AA is a rare, dose independent, irreversible, idiosyncratic, manifestation of CAP which in most cases is seen years after the treatment (A. A. Younis, 1989 (a)) and is fatal (A. A. Turton, et al., 2002) risk of developing AA after CAP administration is 1:30000 to 1:5000015 (C. H. Li, et al., 2010). Only orally administered CAP leads to AA (R. Holt, 1967; R. A. Gleckman, 1975). This has made the CAP to be prescribed parenterally by many physicians. It is not known whether this lowers the incidence of AA or not but the risk is obviously lowered. Other than oral and parenterally absorbed CAP, it is also used as ophthalmic preparations where AA is also very rare (R. L. Rosenthal and A. Blackman, 1965;G. Carpenter, 1975; S. M. Abrams, et al., 1980) Blood or hematological parameters are probably the more rapid and detectable variations under stress and are fuel in assessing different health conditions (V. Hymavathi ) have been reported to express a positive impact on the hematological profile of several animal species. Assessment of hematological parameters can therefore be useful in determining the extent of deleterious effects of foreign substances on the blood parameters of an animal. The present investigation was therefore aimed at assessing the effect of Chloramphenicol on the hematological profile in Charles Foster male rats. II.

2. Materials and methods a) Administration of Material

The chloramphenicol Capsules IP manufactured by Piramal Health Care Limited (Batch No-9BE012) were used for the study. Freshly prepared chloramphenicol suspension was administered orally by cannula for 24 days.

3. b) Animals

Albino rats of Charles Foster strain were used in the study. IAEC approval number was taken from the Institutional Animal House Facility which is affiliated to and works under the guidelines of CPCSEA (No. 36/11/Toxicol/IAEC). Rats weighed between 120-150 grams and were housed in polypropylene, autoclavable cages (dimensions: 43x27x15 cm) with steel wire-mesh lid having provisions for attaching water bottle and for keeping food pellets. Animals had continuous access to food and water during the entire period of experimentation. They were examined routinely for their body weights and hematological parameters.

4. c) Experimental Design

20 rats showing evidences of good health were selected on the basis of findings of their initial health check-up and body weight recordings. They were randomly assigned to four treatment groups, each group consisting of five male animals and one group comprising of an equal number of animals served as control.

Group

5. e) Statistical Analysis

All data was analyzed by applying One way ANOVA with the p value limits of 0.05. Software used for the purpose was PRISM.

6. III.

7. Results

The result of this study, on the effect of oral dosing of CAP on the hematological parameters in rats is presented in Table 1 and 2. The results showed that the hemoglobin (Hgb), Red Blood Cells (RBC) count, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC) obtained for rats administered with CAP orally were significantly (p<0.05) lower in a dose-dependent pattern, compared to the control (Tables 1 and 2). On the contrary, the total White Blood Cells (WBC), platelets and Hematocrit (Hct) levels obtained for rats administered with CAP orally following the same pattern, were significantly (p<0.05) higher, compared to the control. IV.

8. Discussion

Hematological profiles are known to provide important information about the environment of a given organism. The results of this present investigation showed that oral exposure to CAP caused a significant decrease in Hgb, RBC, MCV and MCHC, whereas increase in Hct, WBC and Platelets. Similar effects on hematological parameters have been reported for such other drugs as Chlorpyrifos (Y. Baig, 2007) and Deltamethrin (S. H. Kowalczyk-Bronisz, et al., 1990). The hematotoxic condition may results from different mechanisms, including decrease in the rate of blood cells synthesis and/or increase in the rate of blood cells destruction. The observed decrease in RBC count, Hgb, MCH and MCHC may therefore, may assumed to be associated with retarded hemopoeisis, destruction and shrinkage of RBC.

Increase in total white blood cells and platelets, as well as increase in Hct, is also reported in this study. The increase in total white blood cells and lymphocyte observed in this work may be suggested to be due to stimulated lymphopoiesis and/or enhanced release of lymphocytes from lymph myeloid tissue (B. K. Das and S. C. Mukherjee, 2003). This lymphocyte response might be a direct stimulatory effect of toxic substances on lymphoid tissues. Alternatively, this response may be assumed to be associated with the drug induced tissue damage and disturbance of the non-specific immune system leading to increased production of leukocytes.

Researchers have reported that CAP induce and enhances some defects which results in damage to undifferentiated marrow stem cells (E. P. Cronkite, 1964). Other researchers suggested that certain enteric bacteria can produce a specific enzyme that degrades CAP to a toxic product (R. Holt, 1967). This was suggested by further studies, which suggests that the metabolites of CAP generated by intestinal bacteria undergo further metabolic transformations in system with in situ production of toxic intermediate (A. A. Yunis, 1989 (a)). In a study (A. A. Yunis, 1973 (b)) it was actually revealed that the p-nitrosulfathiazole group is responsible for CAP induced hematotoxicity by inhibiting DNA synthesis in marrow stem cells. This theory was based on the observation that thiamphenicol which is a CAP derivative, does not have a p-nitrosulfathiazole group and does not cause hematotoxicity and thus, extensively used in Europe. This theory was further supported by studies indicating CAP reduced to pnitrosulfathiazole which is a short lived reduction intermediate and leads to helix destabilization and strand breakage (M. Irena, et al., 1983) except than being unstable these intermediates are highly toxic (P. Eyer, et al., 1984). At a concentration of 2000-4000 µg/ml CAP depressed phagocytosis and burst activity of neutrophils (M. J. Paape, et al., 1990). Other studies suggests that CAP directly induce apoptosis in hematopoietic stem cells, directly leading to hematotoxicity (C. I. Kong, et al., 2000).

V.

9. Conclusion

In conclusion, significant adverse changes in hematological parameters are reported to be associated with exposure to CAP, in this present study. This therefore suggest that exposure to CAP may be considered to be among the risk factors for the development of anaemic condition. Hence, exposure to this drug should be minimized.

Figure 1.
, 2011), Paclitaxel (J. A. Juaristi, et al., 2001), Carbamazepine (S. Thakur, et al., 2012), Doxorubicin (D. A. Eppstein, et al., 1989), Tetrachloroethylene (A. M. Emara et al., 2010), Phenacetin (C. B. Jensen and D. J. Jollow 1991) and Benzene (A. Beamonte et al., 2005; R. Synder and C. C. Hedli, 1996). Plants also have been shown to have ameliorative potential in reference to drug induced hematotoxicity (F. S. Sanni et al., 2005; E. E. Edet et al., Volume XIII Issue IV Version I Authors ? ? : Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, India -226031. E-mail : rktox@yahoo.com 2011; E. V. Ikpeme et al., 2011; S. O. Kolawole et al., 2011, G. Prasad and G. L. Priyanka, 2011). Different
Figure 2. Table 1 :
1
Gp Treatment Hgb RBC Hct MCV MCHC WBC Platelets
Gp. I Control, 11.88±0.51 7.09±0.54 44.44±2.68 62.80±2.29 26.70±0.67 7.02±1.15 530.00±112.84
D.W.
Gp. II 750 mg/g 12.30±0.51 6.97±0.69 46.22±5.57 66.28±3.87 26.78±2.64 9.93±2.05 331.00±145.74
b.wt
Gp. III 1500 mg/kg 12.92±0.26 7.81±0.75 52.18±3.44 66.96±2.88 24.74±1.13 10.70±2.79 339.00±162.06
b.wt
Gp. IV 2250 mg/kg 12.52±0.63 7.65±0.68 48.82±3.99 63.88±1.65 23.98±5.35 10.40±3.60 391.00±52.72
b.wt
Note: Data are presented as Mean±S.D., n=5, p< 0.05 compared to control.
Figure 3. Table 2 :
2
Gp Treatment Hgb RBC Hct MCV MCHC WBC Platelets
Gp. I Control, 10.42±0.30 6.96±0.38 50.48±2.53 56.42±2.27 24.62±1.39 17.94±3.62 560.20±126.80
D.W.
Gp. II 750 mg/kg 11.62±0.57 5.67±0.57 55.82±5.14 58.48±1.73 24.98±0.92 16.92±3.81 339.40±28.38
b.wt
Gp. III 1500 10.12±1.29 7.20±0.75 55.28±5.14 60.12±2.37 22.96±1.63 17.58±5.27 419.40±127.18
mg/kg b.wt
Gp. IV 2250 11.26±0.40 6.24±0.75 51.98±3.73 56.32±2.24 23.64±1.11 17.12±3.34 397.40±9.63
mg/kg b.wt
Data are presented as Mean±S.D., n=5, p< 0.05 compared to control.
1
2
3
4
2
6

Appendix A

  1. Yunis (1989 (a) Chloramphenicol toxicity: 25 years of research. AA . Am. J. Med 3 p. .
  2. Yunis (1973 (b) Chloramphenicol -induced bone marrow suppression. AA . Semin. Hematol 10 p. .
  3. Haematologic and hepatic enzyme alterations associated with acute administration of Antiretroviral drugs. A A A Kayode , O T Kayode , O A Aroyeun , M C Stephen . J. Pharmacol. Toxicol 2011. 6 p. .
  4. Studies on haematotoxicity of chloramphenicol succinate in Dunkin Hartley guinea pig. A A Turton , C M Andrews , A C Harvard , T C Williams . Int. J. Exp. Pathol 2002. 5 p. .
  5. A case of drug-induced hematotoxicity: from in vivo to in vitro assessment. A Beamonte , F Goldfain-Blanc , N Casadevall , D Bazot , H Bertheux , N Claude . Comp Clin. Path 2005. 14 p. .
  6. Haematological changes in rat, Rattus rattus after repeated exposure to thiodan 35. A K Solanke , V H Singh . EC. Environ. Ecol 2000. 18 p. .
  7. Antioxidant effects of whole ginger (Zingiber officinale Roscoe) against lead acetateinduced hematotoxicity in rats. A M M Attia , F A A Ibrahim , G M Nabil , S W Aziz . J. of Med. Plants Res 2013. 7 (17) p. .
  8. Immunotoxicity and hematotoxicity induced by tetrachloroethylene in egyptian dry cleaning workers. A M Emara , M M A El-Noor , N A Hassan , A A Wagih . Inhal. Toxicol 2010. 22 (2) p. .
  9. Effect of Hibiscus sabdariffa anthocyanins on 2, 4-dinitrophenylhydrazine-induced tissue damage in rabbits. A Ologundudu , A O Ologundudu , O M Oluba , I O Omotuyi , F O Obi . J. Toxicol. Environ. Health 2010. (1) p. .
  10. ) the effects of aqueous Ocimum gratissimum leaf extract on some biochemical and hematological parameters in male mice. A W Obianime , J S Aprioku , C Esomonu . Asian J. Biol. Sci 2011. 4 p. .
  11. Toxicity of cypermethrin in Labeo rohita fingerlings: Biochemical enzymatic and haematological consequence. B K Das , S C Mukherjee . Comp. Biochem. Physiol. Toxicol. Pharmacol 2003. 134 p. .
  12. Jollow (1991) the role of Nhydroxyphenetidine in phenacetin-induced hemolytic anemia. C B Jensen , DJ . Toxicol. Appl. Pharmacol 111 (1) p. .
  13. Metabolism of chloramphenicol succinate in human bone marrow. C E Ambeker , B Cheung , J Lee , L C Chan , R Liang , C R Kumana . Eur. J. Clin. Pharmacol 2000. 56 p. .
  14. Chloramphenicol causes mitochondrial stress , decresases ATP biosynthesis, induces matrix metalloproteinase -13 expression, and solid tumor cell invasion. C H Li , Y W Cheng , P L Liao . Toxicol Sci 2010. 116 (1) p. .
  15. Effects of antioxidants and a caspase inhibitor on chloramphenicol induced toxicity on human bone marrow and HL 60 cells. C I Kong , D E Holt , S K Ma , A K Lie , L C Chan . Hum. Exp. Toxicol 2000. 19 (9) p. .
  16. Prevention of Doxorubicin-induced Hematotoxicity in Mice by Interleukin 1. D A Eppstein , C G Kurahara , N A Bruno , T G Terrell . Cancer Res 1989. 49 p. .
  17. Bacterial protein synthesis: the effects of antiobiotics. E Cundliffe , K Mcquillen . J. Mol. Biol 1967. 30 p. .
  18. Gongronema latifolium crude leaf extract reverses alterations in haematological indices and weightloss in diabetic rats. E E Edet , M I Akpanabiatu , F E Uboh , T E Edet , A E Eno , E H Itam , I B Umoh . J. Pharmacol. Toxicol 2011. 6 p. .
  19. Enigmas underlying study of haemopoietic cell proliferation. E P Cronkite . Fad. Proc 1964. 23 p. .
  20. Kooffreh and 0. Udensi (2011) Phytochemistry and haematological potential of ethanol seed, leaf and pulp extracts of Carica papaya (Linn.). Pak. E V Ikpeme , U B Ekaluo , ME . J. Biol. Sci 14 p. .
  21. Effect of inhalation exposure to kerosene and petrol fumes on some anaemia-diagnostic indices in rats. F E Uboh , P E Ebong , O U Eka , E U Eyong , M I Akpanabiatu . Global J. Environ. Sci 2005. 3 p. .
  22. Effect of oral administration of aqueous extract of Khaya senegalensis stem bark on phenylhydrazine-induced anaemia in rats. F S Sanni , S Ibrahim , K A N Esievo , S Sanni . Pak. J. Biol. Sci 2005. 8 p. .
  23. Haematinic activity of Hibiscus cannabinus. G A Agbor , J E Oben , J Y Ngogang . Afr. J. Biotech 2005. 4 (8) p. .
  24. Chloramphenicol eye drops and marrow aplasia. G Carpenter . Lancet 1975. 2 p. .
  25. Metabolic study discussion on chloramphenicol, G Milhaud . 1983. (WHO report)
  26. Effect of rind extract of Garcnia gummi-gutta on haematology and plasma biochemistry of Catfish, Pangasianodon hypophthalmus. G Prasad , G L Priyanka . Asian J. Biochem 2011. 6 p. .
  27. Hematotoxicity induced by paclitaxel: in vitro and in vivo assays during normal murine hematopoietic recovery. J A Juaristi , M V Aguirre , R J Carmuega , M Romero-Benitez , M A Alvarez , N C Brandan . Methods Find Exp Clin Pharmacol 2001. 23 (4) p. .
  28. Phenylhydrazine Haematotoxicity. J Berger . J. Appl. Biomed 2007. 5 p. .
  29. Responses of cypermethrin-induced stress in haematological parameters of Korean rockfish, Sebastes schlegeli (Hilgendorf). L H Jee , F Masroor , J C Kang . Aquacult. Res 2005. 36 p. .
  30. Pesticidal residue analysis of organochlorine residues in different milk samples from Chittoor district in Andhra Pradesh, India. Final Report of UGC Minor Research Project during the Period from, M D A Baig . 2007. 2004-2006.
  31. Hematological and clinical chemistry changes induced by subchronic dosing of a novel phosphorothion ate (RPR-V) in Wistar male and female rats. M F Rahman , M K Siddiqui . Drug Chem. Toxicol 2006. 29 p. .
  32. Molecular basis of chloramphenicol and thiamphenicol toxicity to DNA in vitro. M Irena , R C Skolimowski , D I Knight , Edwards . J. Antimicrob. Chemother 1983. 12 (6) p. .
  33. In vivo effects of chloramphenicol, tetracycline, and gentamicin on bovine neutrophil function and morphologic features. M J Paape , S C Nickerson , G Ziv . Am. J. Vet. Res 1990. 51 p. .
  34. A fatal case of aplastic anemia following chloramphenicol (chloromycetin) therapy. M L Rich , R J Ritterhoff , R J Hoffman . Ann. Inter. Med 1950. 33 p. .
  35. Effect of short term endosulfan on hematology and serum analysis of male rat. N Choudhary , S C Joshi . Indian J. Toxicol 2002. 9 p. .
  36. Ezike (2009) the haematinic activity of the methanol leaf extract of Brillantasia nitens Lindau (Acanthaceae) in rats. P A Akah , C E Okolo , AC . Afr. J. Biotech 8 (10) p. .
  37. Aqueous extract and methanol fractions of the leaves of Brillantasia nitens Lindau. Reverses phenylhydrazine -induced anaemia in rats. P A Akah , C E Okolo , T C Okoye , N V Offiah . J. Med. Plants Res 2010. 4 (3) p. .
  38. Reactions of nitrosochloramphenicol in blood. P Eyer , E Lierheimer , M Schneller . Biochem. Pharmacol 1984. 33 p. .
  39. Warning-chloramphenicol may be good for your health. R A Gleckman . Arch. Intern. Med 1975. 135 p. .
  40. ) the bacterial degradation of chloramphenicol. R Holt . Lancet 1967. 1 p. .
  41. Bone marrow hypoplasia following use of chloramphenicol eyedrops. R L Rosenthal , A Blackman . J. A. M. A 1965. 191 p. .
  42. Hedli (1996) an overview of benzene metabolism (Review). R Synder , CC . Environ. Health Perspect 104 p. .
  43. Immunological profile of animals exposed to pesticide--deltamethrin. S H Kowalczyk -Bronisz , J Gieldanowaki , B Bubak . Arch. Immunol. Ther. Exp (Warsz) 1990. 38 (3 -4) p. .
  44. on the mechanism of phenylhydrazine-induced hemolytic anemia. S K Jain , D Subrahmanyam . Biochem. Bioph. Res. Co 1978. 82 (4) p. .
  45. Marrow aplasia following topical application of chloramphenicol eye ointment. S M Abrams , T J Degnan , V Vinciguerra . Arch. Intern. Med 1980. 140 p. .
  46. Effect of aqueous extract of Kkaya senegalensis stem bark on biochemical and haematological parameters in rats. S O Kolawole , O T Kolawole , M A Akanji . J. Pharmacol. Toxicol 2011. 6 p. .
  47. Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice. S Saha , M K Mukhopadhyay , P D Ghosh , D Nath . 10.1155/2012/176385. Evid. Based Complement. Alternat. Med 2012.
  48. Amelioration of carbamazepine induced oxidative stress and hematotoxicity by vitamin C. S Thakur , M Eswaran , S G Rajalakshmi . Spatula DD 2012. 2 (3) p. .
  49. Effect of chlorpropham (CIPC) on the hemopoietic system of rats. T Fujitani , Y Tada , A T Noguchi , M Yoneyama . Food Chem. Toxicol 2001. 39 p. .
  50. Effect of sublethal concentrations of lead on the haematology and biochemical constituents of Channa punctatus. V Hymavathi , L M Rao . Bulletin Pure Applied Sci 2000. 19 p. .
  51. Changes in hematological profiles of albino rats under chlorpyrifos toxicity. Y Savithri , P R Sekhar , P J Doss . Int. J. Pharma. Bio. Sci 2010. 1 p. .
Notes
1
© 2013 Global Journ © 2013 Global Journals Inc. (US)
2.
( )B
3
© 2013 Global Journals Inc. (US)
4
© 2013 Global Journ © 2013 Global Journals (US)
2.
( )B
6
( )B
Home 
Date: 2013-01-15