Effect of Phenobarbital on Chloramphonicol-Induced Toxicity in Rat Liver and Small Intestine

Authors

1 Physiology, Toxicology and Social Determinants of Health Research Centers of Ahvaz,Occupational Health Department of Public Health School, , Ahvaz Jundishapur

2 Occupational Health Department of Public Health School, , Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

 




Objective(s):
The aim of the present study is to determine the effect of Chloramphenicol (CAP) on rat liver and small intestine. Effect of phenobarbital (PB) on CAP toxicity was also investigated.
 
Materials and Methods:
 
Rats were received CAP at doses of 0, 200, 400 and 600 mg/kg. Another group was pretreated with 80 mg/kg PB 30 min prior to administration of various doses of CAP. The experiment was repeated for seven consecutive days. Blood was collected for determination of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT). The liver and small intestine tissues were processed for light microscopy.
 
Results:
 
CAP induced a dose dependent elevation of AST and ALT and produced injury in the liver and small intestine when compared to control animals. PB markedly decreased AST and ALT levels and protected liver and small intestine against CAP-induced toxicity.
 
Conclusion
 
: This study suggested rat liver and small intestine have potential to bioactivate CAP.

Keywords


1. Ruef C, Blaser J. Miscellaneous antibacterial drugs: aminoglycosides, chloramphenicol and thiamphenicol, fluoroquinolones, glycopeptides. In: Dukes MNG, Aronson JK, editors. Meyler’s side effects of drugs. The Netherlands: Elsevier Sciences; 2000.p.848-851.

2. Turton JAD, Yallop CM, Andrews R, Fagg M, York M, Williams TC. Haemotoxicity of chloramphenicol succinate mouse and Wistar Hanover rat.Human ExpToxicol 1999; 18:566-67.

3. Hammett-Stabler CA, Johns T. Laboratory guidelines for monitoring of antimicrobial drugs. Clin Chem1998; 44:1129–1140.

4. Kao LP, Ovchinnikov D, Wolvetang E. The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts.ToxicolApplPharmacol 2012; 261:42-49.

5. Shukla P, Bansode FW, Singh RK. Chloramphenicol toxicity: A review. J Med Sci 2011; 2:1313-1316.

6. Esimone CO, Nworu CS, Ekechukwu AC, Awemu AG. Effect of phenylalanine and glycine on some toxic effects of chloramphenicol. Sci Res Essay 2007; 2:105-111.

7. Effiong GS, Ebong PE, Eyong EU, Uwah AJ, Ekong UE. Amelioration of chloramphenicol Induced toxicity in rats by coconut water. J App Sci Res 2010; 6:331-335.

8. Saba AB, Ola-davies O, Oyeyem MO, Ajala O. The toxic effects prolonged administration of chloramphenicol on the liver and kidney of rats. Afr J Biomed Res 2000; 3:133-137.

9. Cybulska R, Jaworska-Adamu J, Cybulski W. Effect of chloramphenicol on the activity of alkaline phosphatase and the structure of microvilli of the epithelial cells of the small intestine of the hen. Folia Histochem Cytobiol 1988; 26:257-261.

10. PrevendarCrnic A, Pomp-Gotal J, Bozic F, Suran J, Velev R, Sakar D. The effect of chloramphenicol on hepatic biotransformation enzyme activity and on the duration of pentobarbital or ketamine/xylazine anesthesia in guinea pigs (CaviaPorcellus). Vet Archive 2009; 79:385-396.

11. Krizkova J, Burdova K, Hudecek J, Stiborova M, Hodek P. Induction of cytochromes P450 in small intestine by chemopreventive compounds. Neuro Endocrinol Lett 2008; 5:717-721.

12. Kaminsky LS, FascoM J. Small intestinal cytochrome p450.Crit RevToxicol 1992; 21:407-422.

13. Hashizume T, Imaoka S, Hiroi T, Terauchi Y, ToshihikoFujii T, Miyazaki H,

et al. cDNA cloning and expression of a novel cytochrome P450 (CYP4F12) from human small intestine. Biochem Biophys Res Commun 2001; 280:1135-1141.

14. Bonkovsky HL, Hauri HP, Marti U, Gasser R, Meyer UA. Cytochrome p450 of small intestinal epithelial cells. Immunochemical characterization of increase in cytochrome p450 caused by Phenobarbital. Gastroenterology 1985; 88:458-467.

15. Palmer DL, Despopoulos A, Rael ED. Induction of chloramphenicol metabolism by Phenobarbital. Antimicrob Agent Chem 1972; 1:112-115.

16. Ahmadizadeh M, Nasiri M. The effect of omeprazole on rat liver and small intestine. Biochem Cell Arch 2006; 6:309-316.

17. Tawfik M, Al-Hussainy MI, Al-Dahan A, Al-Zubaidy J. Choramphenicol induced pathological alterations in the intestinal epithelium. Pharm Res Commun 1979; 11:199-209.

18. Halpert J, Naslund B, Betner I. Suicide inactivation of rat liver cytochrome p450 by chloramphenicol

in vivo and in vitro. Mol Pharm 1983; 23:445-452.

19. Shaik IH, Mehvar R. Cytochrome p450 induction by phenobarbital exacerbates warm hepatic ischemia-reperfusion injury in rat livers. Free Radic Res 2010; 44:441-453.