Effects of Ciprofloxacin and Levofloxacin Administration on Some Oxidative Stress Markers in the Rat

Fluoroquinolones are a group of antibiotics widely used because of their broad spectrum activity against both Gram-positive and Gram-negative bacteria. In this study, ciprofloxacin and levofloxacin were administered to rats at therapeutic doses to evaluate their effects on plasma arylesterase activity, as well as, on hepatic advanced oxidized protein products (AOPPs) and malondialdehyde (MDA) levels, as measures of oxidative stress. Ciprofloxacin (80 mg/kg body weight) and levofloxacin (40 mg/kg body weight) were administered to male albino rats for 7 and 14 days. The data obtained demonstrated that plasma arylesterase activity was significantly decreased by both drugs with ciprofloxacin administration inhibiting the activity by 29% and 30% while Levofloxacin treatment resulted in 35% and 30% inhibition, after 7 and 14 days treatment respectively. Hepatic AOPP and MDA levels were both elevated by these antibiotics. This study supplies further evidence that fluoroquinolones at therapeutic doses promote oxidative stress.





References:
[1] C. M. Oliphant and G. M. Green. Quinolones: a comprehensive review. Am. Fam. Physician, 2002, 66 (3):455-464.
[2] S. Shenoy, S. Chakravarty, A. Nayak, P. Z. Candita, T. Shanbhag. Anxiogenic effect of moxifloxacin in wistar rats. Inter. J. Appl. Biol. Pharm. Tech. 2011, 3 (4):158-162.
[3] L. B. Laurence and K. L. Parker. Ciprofloxacin in chemotherapy of microbial diseases. Academic Press, New York, 2008, pp. 709-839.
[4] J. M. Blondeau. Expanded activity and utility of the new fluoroquinolones: a review. Clin. Ther. 1999, 21: 3-40.
[5] T. D. Gootz, J. F. Barret, H. E. Holden, V. A. Ray, P. R. McGuirk. Selective toxicity: the activity of 4-quinolones against eukaryotic DNA topoisomerase. In G. Crumplin (ed.) The 4-quinolones: antibacterial agents in vitro. London: Springer-Verlag, 1990, pp. 159-171.
[6] N. S. Kumar, D. Dhivya and B. Vijayakumar. A focus on quinolones and its medicinal importance. Inter. J. Novel Trends Pharm. Sciences; 2011, 1 (1): 23-29.
[7] J. S. Wolfson and D. C. Hooper. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob. Agents Chemother. 1985, 28: 581-586.
[8] M. L. Grayson. Ciprofloxacin. In Kucers A, Crowe SM, Grayson ML, Hoy JF eds. The use of antibiotics: a clinical review of antibacterial, antifungal, and antiviral drugs. Avon: The Bath Press, 1999, pp. 981-1060.
[9] B. Halliwell, J. M. C. Gutteridge. Oxidative stress: adaptation, damage, repair and death. In: Halliwell B, Gutteridge JMC, editors. Free radicals in biology and medicine. Oxford, UK: Oxford University Press; 1999, pp. 284–330.
[10] S. M. Zaidi and N. Banu. Antioxidant potential of vitamins A, E and C in modulating oxidative stress in rat brain. Clin. Chim. Acta; 2004, 340: 229–33.
[11] A. Y. Sun and Y. M. Chen. Oxidative stress and neurodegenerative disorders. J. Biomed. Sci., 1988, 5: 401-414.
[12] P. M. Abuja and R. Albertini. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clinica Chimica Acta 2001, 306: 1–17.
[13] Guidance for Industry and Reviewers. Estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers. Food and Drug Administration, 2002, pp. 1-26.
[14] W. Junge, H. Klees. 1,2-Arylesterase. Methods Enzym. Anal., 1984, 4: 8-14.
[15] H. Ohkawa, N. Ohishi, K. Yagi. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Annal of Biochemistry; 1979, 95: 351-358.
[16] V. Witko-Sarsat, M. Friedlander, C. Capeille`re- Blandin, T. Nguyen-Khoa, A. T. Nguyen, J. Zingraff, P. Jungers, and B. Descamps-Latscha. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int., 1996, 49: 1304-1313.
[17] M. E. Buyukokuroglu, M. Cemek, Y. Yurumez, Y. Yavuz, A. Aslan. Antioxidative role of melatonin in organophosphate toxicity in rats. Cell Biol. Toxicol. 2008, 24: 151–158.
[18] B. Halliwell, J. M. C. Gutterridge. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1994, 1: 1396–1397.
[19] A. Valenzuela. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci. 1990, 48: 301–309.
[20] J. Chaudiere, R. Ferrari-Iliou. Intracelluler antioxidants: from chemical to biochemical mechanisms. Food Chem. Toxicol. 1999, 37: 949–962.
[21] D. W. J. Clark, L. Deborah, V. W. Lynda, L. P. Gillian and A. W. S. Saad. Profiles of hepatic and dysrhythmic cardiovascular events following use of fluoroquinolone antibacterials: Experience from large cohorts from the drug safety research unit prescription monitoring database. Drug Safety, 2001, 24: 1143-1154.
[22] V. R. Dhamidharka, Nadeau, C. L. cannon, H. W. Harris and S. Rosen. Ciprofloxacin overdose: Acute renal failure with prominent apoptotic changes. Am J Kid Dis. 1998, 31: 710-712.
[23] F. Pouzauaud, M. Dutot, C. Martin, M. Debray, J. M. Warnet and P. Rat. Age-dependent effects on redox status, oxidative stress, mitochondrial activity and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon cells. Comp Biochem Physiol. C. Toxicol Pharmacol. 2006, 143: 232-241.
[24] S. Altınordulu, G. Eraslan. Effects of some quinolone antibiotics on malondialdehyde levels and catalase activity in chicks. Food Chem. Toxicol. 2009, 47: 2821–2823.
[25] P. L. Páez, M. C. Becerra and I. Albesa. Comparison of macromolecular oxidation by reactive oxygen species in three bacterial genera exposed to different antibiotics. Cell Biochem Biophys. 2011, 61 (3): 467-472.
[26] I. Albesa, M. C. Beccera, P. C. Baattán and P. L. Páez. Oxidative stress involved in the antibacterial action of different antibiotics. Biochem Biophys Res Commun. 2004, 317 (2): 605-609.
[27] C. Alderman, S. Shah, J, C. Foreman, B. M. Chain and D. R. Katz. The role of advanced oxidation protein products in regulation of dendritic cell function. Free Radic Biol Med 2002, 32: 377–385.
[28] C. Penna, D. Mancardi, R. Rastaldo, et al., Cardioprotection: a radical view: free radicals in pre and postconditioning. Biochim Biophys Acta 2009, 1787: 781-793.
[29] L. Zy, B. Liu, J. Yu, F. W. Yang, Y. N. Luo and P. F. Ge. Ischaemic postconditioning rescues brain injury caused by focal ischaemic/reperfusion via attenuation of protein oxidation. The journal of International Medical Report. 2012, 40: 954-966.
[30] A. Gürbay, C. Garrel, M. Osman, M. J. Richard, A. Favier, F. Hincal. Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E. Hum. Exp. Toxicol. 2002, 21: 635-641.
[31] F. Sörgel. Metabolism of gyrase inhibitors. Rev Infect Dis 1989, 11 (Suppl): S1119-1129.
[32] M. Aviram, M. Rosenblat. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med; 2004, 37: 1304–1316.
[33] B. N. La Du, N. Aviram, S. Billecke, M. Navab, S Primo-Parmo, R. C. Sorenson and T. J. Standiford. On the physiological role(s) of the paraoxonases. Chemical and Biological Interaction, 1999, 119–120: 379–388.
[34] P. N. Durringhton, B. Mackness, M. J. Mackness. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001, 21: 473–480.
[35] S. Sinan, F. Kockar, N Gencer, H. Yildirim and O. Arslan. Amphenicol and macrolide derived antibiotics inhibit paraoxonase enzyme activity in human serum and human hepatoma Cells (HepG2) in vitro. Biochemistry (Moscow), 2006, 71: 46–50.
[36] F. Kockar , S. Sinan, H. Yildirim, O. Arslan. Differential effects of some antibiotics on paraoxonase enzyme activity on human hepatoma cells (HepG2) in vitro. Journal of Enzyme Inhibition and Medicinal Chemistry, 2010, 25 (5): 715–719.
[37] M. Aviram, M. Rosenblat, S. Billecke, J. Erogul, R. Soreson, C. L. Bisgaier, Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radicals in Biological Medicine, 1999, 26: 892–904.
[38] O. Rozenberg, M. Aviram M. S-Glutathionylation regulates HDL-associated paraoxonase 1 (PON1) activity. Biochem. Biophys. Res. Commun. 2006, 351 (2): 492-498.
[39] B. N. La Du. Human serum paraoxonase/arylesterase. In: Kalow W, ed. Pharmacogenetics of Drug Metabolism. New York, NY: Pergamon Press; 1992, pp. 51–91.
[40] M. I. Mackness, S. Arrol, C. Abbott and P. N. Durrington. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis; 1993, 104: 129–135.