Aliye Aliye ÖZTÜRK SAĞKAN, Ramazan DURGUT, Oktay Hasan ÖZTÜRK, Ahmet NACAR

Cardiotoxic effects of enrofloxacin on electrophysiological activity, cardiac markers, oxidative stress, and haematological findings in rabbits

The aim of this research was to investigate the effect of normal and high doses of enrofloxacin on basal electrocardiographic (ECG) parameters including corrected QT (QTc) values along with biochemical and haematological findings in healthy rabbits. In total 21 New Zealand rabbits were used. The animals were randomly divided into three groups including 7 rabbits in each. The normal dose (5 mg/kg) of enrofloxacin and a toxic dose (50 mg/kg) were given intravenously in group 1, and the normal dose was given for 6 weeks in group 2. The last group was designated as a negative control (group 3). ECG, serum biochemistry parameters, and total antioxidant capacity (TAC) and total oxidant status (TOS) were determined every week. At the end of the experiment, necropsy was performed and histology was evaluated. Some oxidative parameters were measured in the heart tissue. No cardiotoxic effect was observed on ECG, in biochemical or haematological findings, or macroscopic or histological findings in groups 2 and 3. The results indicated that enrofloxacin is not harmful for the heart in clinically healthy rabbits at normal and toxic doses compared with the negative control group in terms of ECG, biochemical or haematological findings, or macroscopic or histological findings.

PDF

___

Abi-Gerges N, Philp K, Pollard C, Wakefield I, Hammond TG, Valentin JP (2004). Sex differences in ventricular repolarization: from cardiac electrophysiology to torsades de pointes. Fundam Clin Pharmacol 18: 139-151.
Apple FS, Falahati A, Paulsen PR, Miller EA, Sharkey SW (1997). Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin i. Clin Chem 43: 2047-2051.
Bertino J Jr, Fish D (2000). The safety profile of the fluoroquinolones. Clin Ther 22: 798-817; discussion 797.
Camm AJ (2005). Clinical trial design to evaluate the effects of drugs on cardiac repolarization: Current state of the art. Heart Rhythm 2: S23-29.
Carlsson L, Abrahamsson C, Andersson B, Duker G, Schiller-Linhardt G (1993). Proarrhythmic effects of the class iii agent almokalant: importance of infusion rate, qt dispersion, and early afterdepolarisations. Cardiovasc Res 27: 2186-2193.
De Ponti F, Poluzzi E, Montanaro N (2001). Organising evidence on qt prolongation and occurrence of torsades de pointes with non-antiarrhythmic drugs: a call for consensus. Eur J Clin Pharmacol 57: 185-209.
Devreese M, Antonissen G, De Baere S, De Backer P, Croubels S (2014). Effect of administration route and dose escalation on plasma and intestinal concentrations of enrofloxacin and ciprofloxacin in broiler chickens. BMC Vet Res 10: 289.
Dickinson DA, Forman HJ (2002). Cellular glutathione and thiols metabolism. Biochem Pharmacol 64: 1019-1026.
Durgut R, Ataseven VS, Sagkan-Ozturk A, Ozturk OH (2013). Evaluation of total oxidative stress and total antioxidant status in cows with natural bovine herpesvirus-1 infection. Journal of Animal Science 91: 3408-3412.
Elmas M, Yazar E, Uney K, Er Karabacak A (2006). Influence of Escherichia coli endotoxin-induced endotoxaemia on the pharmacokinetics of enrofloxacin after intravenous administration in rabbits. J Vet Med A Physiol Pathol Clin Med 53: 410-414.
Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 37: 112-119.
Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38: 1103-1111.
Frothingham R (2001). Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 21: 1468-1472.
Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A et al. (2000). The potential for qt prolongation and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a policy conference of the European Society of Cardiology. Eur Heart J 21: 1216-1231.
Kijtawornrat A, Ozkanlar Y, Keene BW, Roche BM, Hamlin DM, Hamlin RL (2006). Assessment of drug-induced qt interval prolongation in conscious rabbits. J Pharmacol Toxicol Methods 53: 168-173.
Loscalzo J, Welch G (1995). Nitric oxide and its role in the cardiovascular system. Prog Cardiovasc Dis 38: 87-104.
Lykkesfeldt J, Svendsen O (2007). Oxidants and antioxidants in disease: oxidative stress in farm animals. Vet J 173: 502-511.
Owens RC Jr. (2001). Risk assessment for antimicrobial agent-induced qtc interval prolongation and torsades de pointes. Pharmacotherapy 21: 301-319.
Owens RC Jr, Ambrose PG (2002). Torsades de pointes associated with fluoroquinolones. Pharmacotherapy 22: 663-668; discussion 668-672.
Ozkanlar Y, Aktas MS, Turkeli M, Erturk N, Oruc E, Ozkanlar S, Kirbas A, Erdemci B, Aksakal E (2014). Effects of ramipril and darbepoetin on electromechanical activity of the heart in doxorubicin-induced cardiotoxicity. Int J Cardiol 173: 519-521.
Ozkanlar Y, Kijtawornrat A, Hamlin RL, Keene BW, Roche BM (2005a). Acute cardiovascular effects of tacrolimus in the isolated guinea pig heart. J Vet Pharmacol Ther 28: 313-316.
Ozkanlar Y, Nishijima Y, da Cunha D, Hamlin RL (2005b). Acute effects of tacrolimus (fk506) on left ventricular mechanics. Pharmacol Res 52: 307-312.
Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S, Siegl PK, Strang I, Sullivan AT, Wallis R et al. (2003). Relationships between preclinical cardiac electrophysiology, clinical qt interval prolongation and torsade de pointes for a broad range of drugs: Evidence for a provisional safety margin in drug development. Cardiovasc Res 58: 32-45.
Saad SY, Najjar TA, Al-Rikabi AC (2001). The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats. Pharmacol Res 43: 211-218.