DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20200190

Ciprofloxacin and levofloxacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence

Haitham M. Mokhimar, Mohamed M. Kandiel, Aziza A. Amin, Hozaifa K. Elsawah, AbuBakr M. El Mahmoudy

Abstract


Background: Drug-induced reproductive organs toxicities is an important aetiology in investigation of male infertility. The aim is to study levofloxacin effect on male reproductive system in comparison to ciprofloxacin.

Methods: Twenty-five male wister rats weighted 230±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received ciprofloxacin with dose 78.23 mg/kg/day in 2 doses (therapeutic dose). The second group received the double dose of the first group ciprofloxacin. The third group received levofloxacin with dose 39.11 mg/kg/day once daily (OD) (therapeutic dose). The Fourth group received the double dose of the third group levofloxacin. However, the fifth group served as a control and received normal saline with carboxymethylcellulose OD. All treatments were administered orally for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all rats. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.

Results: Ciprofloxacin and levofloxacin negatively altered reproductive organ weights, sperm parameters and serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) level (p<0.05). Additionally, serum testosterone level was significantly deceased in ciprofloxacin-treated group (the double dose) (p<0.05) relative to control. The difference between ciprofloxacin and levofloxacin was significant in seminal vesicle weight and serum LH and FSH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of levofloxacin and ciprofloxacin were dose-dependent.

Conclusions: Both ciprofloxacin and levofloxacin adversely affect andrological function that should be monitored and controlled during application of these drugs.


Keywords


Ciprofloxacin, Levofloxacin, Oxidative, Testis, Sperm, Reproduction, Fertility

Full Text:

PDF

References


Kowalski RP, Dhaliwal DK, Karenchak LM, Romanowski EG, Mah FS, Ritterband DC, et al. Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates. Am J Ophthalmol. 2003;136(3):500-5.

Walker RC, editor The fluoroquinolones. Mayo Clinic Proceedings; Elsevier. 1999.

Krcmery S, Naber K, German Ciprofloxacin U, Group US, Naber K, R Barth M, et al. Ciprofloxacin once versus twice daily in the treatment of complicated urinary tract infections. Int J Antimicrobial Agents. 1999;11(2):133-8.

Humphreys H, Speller D. Acute epididymo-orchitis caused by Pseudomonas aeruginosa and treated with ciprofloxacin. J Infect. 1989;19(3):257-61.

Bundrick W, Heron SP, Ray P, Schiff WM, Tennenberg AM, Wiesinger BA, et al. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology. 2003;62(3):537-41.

Killgore KM, March KL, Guglielmo BJ. Risk factors for community-acquired ciprofloxacin-resistant Escherichia coli urinary tract infection. Ann Pharmacotherap. 2004;38(7-8):1148-52.

Merino G, Carranza-Lira S. Infection and male infertility: effect of different antibiotic regimens on semen quality. Arch Androl. 1995;35(3):209-12.

Al-Tawfiq JA, Momattin H, Hinedi K. Empiric antibiotic therapy in the treatment of community-acquired pneumonia in a general hospital in Saudi Arabia. J Global Infect Dis. 2019;11(2):69.

Chao Y-S, Farrah K. Fluoroquinolones for the Treatment of Urinary Tract Infection: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines. 2019.

Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology. 2008;71(1):17-22.

Nickel JC, Downey J, Clark J, Casey RW, Pommerville PJ, Barkin J, et al. Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial. Urology. 2003;62(4):614-7.

Garthwaite MA, Johnson G, Lloyd S, Eardley I. The implementation of European Association of Urology guidelines in the management of acute epididymo-orchitis. Ann Royal Coll Surgeons Engl. 2007;89(8):799-803.

Ball P. Safety of the new fluoroquinolones compared with ciprofloxacin. J Chemotherap. 2000;12(sup1):8-11.

Farkas A, Woods KL, Ciummo F, Shah A, Sassine J, Olivo Freites C, et al., editors. 1545. Development of a Linear Mixed-Effect Pharmacodynamic Model to Quantify the Effects of Frequently Prescribed Antimicrobials on QT Interval Prolongation in Hospitalized Patients. Open Forum Infectious Diseases; 2019: Oxford University Press US.

Podder V, Sadiq NM. Levofloxacin. StatPearls: StatPearls Publishing; 2019.

Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101-19.

Drusano G, Standiford H, Plaisance K, Forrest A, Leslie J, Caldwell J. Absolute oral bioavailability of ciprofloxacin. Antimicrobial Agents And Chemotherap. 1986;30(3):444-6.

Watanabe T, Fujikawa K, Harada S, Ohura K, Sasaki T, Takayama S. Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits. Arzneimittel-Forschung. 1992;43(3):374-7.

Vicari L, Castiglione R, Salemi M, Vicari B, Mazzarino M, Vicari E. Effect of levofloxacin treatment on semen hyperviscosity in chronic bacterial prostatitis patients. Andrologia. 2016;48(4):380-8.

Al-Dujaily S, Abd AH, Al-Saray DA. Effects of Levofloxacin on Male Reproductive System Parameters and Sperm DNA Normality in Rats. J Pharma Sci Re. 2018;10(3):462-6.

Luthfi MJf. A Simple and Practical Method for Rat Epididymal Sperm Count (Rattus norvegicus). Biol Med Natural Product Chem. 2015;4(1):1-3.

Semet M, Paci M, Saïas‐Magnan J, Metzler‐Guillemain C, Boissier R, Lejeune H, et al. The impact of drugs on male fertility: a review. Andrology. 2017;5(4):640-63.

Staff A. The Optimal Evaluation of the Infertile Male: AUA Best Practice Statement. 2010.

Khaki A. Effect of ciprofloxacin on cauda epididymis sperm quality and apoptosis. J Urmia Univ Med Sci. 2008;19(1):29-35.

Arash K, Peirouvi T. Effect of ciprofloxacin on cauda epididymis sperm quality and apoptosis. J Urmia Univ Med Sci. 2008;19(1):29-35.

Demir A, Türker P, Önol FF, Sirvanci S, Findik A, Tarcan T. Effect of experimentally induced Escherichia coli epididymo‐orchitis and ciprofloxacin treatment on rat spermatogenesis. International journal of urology. 2007;14(3):268-72.

Abd-Allah AR, Aly HA, Moustafa AM, Abdel-Aziz A-AH, Hamada FM. Adverse testicular effects of some quinolone members in rats. Pharmacol Res. 2000;41(2):211-9.

Iqbal R, Iqbal S, Anjum S. Effect of Quinolones on Serum Testosterone Level in Male Albino Rats. Ann King Edward Medical Univ. 2017;23(1).

Zobeiri F, Sadrkhanlou R-A, Salami S, Mardani K. Long-term effect of ciprofloxacin on testicular tissue: evidence for biochemical and histochemical changes. Int J Fertility Sterility. 2013;6(4):294.

Ahmadi R, Ahmadifar M, Safarpour E, Vahidi-Eyrisofla N, Darab M, Eini AM, et al. The effects of levofloxacin on testis tissue and spermatogenesis in rat. Cell J (Yakhteh). 2016;18(1):112.

Laurence DR, Bacharach AL. Evaluation of drug activities: pharmacometrics: ASPET; 1964.

Kerr J. Spontaneous degeneration of germ cells in normal rat testis: assessment of cell types and frequency during the spermatogenic cycle. Reproduction. 1992;95(3):825-30.

Dohle G, Smit M, Weber R. Androgens and male fertility. World J Urol. 2003;21(5):341-5.

Nashwa A, Kawkab AA, Mouneir SM. The protective effect of ginger and N-acetyl cysteine on ciprofloxacin-induced reproductive toxicity in male rats. J Am Sci. 2011;7(7).

Talla V, Veerareddy P. Oxidative stress induced by fluoroquinolones on treatment for complicated urinary tract infections in Indian patients. J Young Pharmacists. 2011;3(4):304-9.

Dym M, Fawcett DW. The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium. Biol Reprod. 1970;3(3):308-26.

Tsuji A, Tamai I. Blood-brain barrier function of P-glycoprotein. Advanced Drug Delivery Rev. 1997;25(2-3):287-98.

Blokhina SV, Sharapova AV, Ol'khovich MV, Volkova ТV, Perlovich GL. Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials. Eur J Pharma Sci. 2016;93:29-37.