Gentamicin and amikacin adversely affect male infertility indicated by pharmacological, andrological and pathological evidence
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20200167Keywords:
Gentamicin, Amikacin, Hormone, Testis, Sperm, ReproductionAbstract
Background: Many drugs are implicated in male infertility and screening for medication history is an important for diagnosis and treatment of the problem. The aim is to study amikacin effect on male reproductive system in comparison to gentamicin.
Methods: Twenty-five male wister rats weighted 220±20 gm and aged 8 weeks were randomly divided into five groups of five. The first group received gentamicin in dose 18.25 mg/kg/day once daily (OD) (therapeutic dose). The second group received gentamicin with double dose of the first group. The third group received amikacin in dose 54.75 mg/kg/day OD (therapeutic dose). The Fourth group received amikacin with double dose of the third group. However, the fifth group served as a control and received normal saline (NS) OD. All treatments were administered intraperitoneally (IP) for 14 days. On the 15th day, blood samples and reproductive organs were obtained from all animals. Testicular tissues were prepared for genetic testing and chemical and microscopical examination.
Results: Amikacin and gentamicin negatively affected reproductive organs weights, sperm parameters, serum follicle stimulating hormone and luteinizing hormone (LH) level relative to control (p<0.05). However, serum testosterone level was only affected with gentamicin (p<0.05). A significant difference between gentamicin and amikacin was found in sperm count, testis and epididymis weights and serum testosterone and LH level (p<0.05). Testicular histopathological changes were also found with the two drugs with different degrees. Effects of both gentamicin and amikacin were dose-dependent.
Conclusions: Both gentamicin and amikacin adversely affect andrological function that should be monitored and controlled during application of these drugs.
References
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-20.
Habib G, Lancellotti P, Antunes MJ, Bongiorni MG, Casalta J-P, Del Zotti F, et al. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). European Heart J. 2015;36(44):3075-128.
Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'grady NP, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(1):1-45.
Davis BD. Mechanism of bactericidal action of aminoglycosides. Microbiol Rev. 1987;51(3):341.
Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: an overview. Cold Spring Harbor Perspect Med. 2016;6(6):a027029.
Kluge RM, Standiford HC, Tatem B, Young VM, Greene WH, Schimpff SC, et al. Comparative activity of tobramycin, amikacin, and gentamicin alone and with carbenicillin against Pseudomonas aeruginosa. Antimicrobial Agents Chemotherap. 1974;6(4):442-6.
Sweileh WM. A prospective comparative study of gentamicin‐and amikacin‐induced nephrotoxicity in patients with normal baseline renal function. Fundamental Clin Pharmacol. 2009;23(4):515-20.
Denamur S, Tyteca D, Marchand-Brynaert J, Van Bambeke F, Tulkens PM, Courtoy PJ, et al. Role of oxidative stress in lysosomal membrane permeabilization and apoptosis induced by gentamicin, an aminoglycoside antibiotic. Free Radical Biol Med. 2011;51(9):1656-65.
Narayana K. An aminoglycoside antibiotic gentamycin induces oxidative stress, reduces antioxidant reserve and impairs spermatogenesis in rats. J Toxicological Sci. 2008;33(1):85-96.
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.
Laurence DR, Bacharach AL. Evaluation of drug activities: pharmacometrics. ASPET; 1964.
Carageorgiou HK, Stratakis CA, Damoulis PD, Varonos DD, Messari ID, Sideris AC, et al. Reversible plasma testosterone levels reduction after gentamicin administration and freund's adjuvant arthritis in rats. Indian J Physiol Pharmacol. 2005;49(4):443.
Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Kim SH, et al. Melatonin prevents gentamicin‐induced testicular toxicity and oxidative stress in rats. Andrologia. 2014;46(9):1032-40.
Sanati E, Nikmanesh M. Comparative study of the effects of gentamicin, neomycin, streptomycin and ofloxacin antibiotics on sperm parameters and testis apoptosis in rats. Pakistan J Biological Sci. 2008;11(13):1683-9.
Akutsu S, Katoh M, Kawana K, Shimamura T, Fukushima Y, Matsuzaki M. Effects of intravenous infusion of amikacin. Intraperitoneal administration to rats before and in the early stage of pregnancy. Segment 1. Japanese J Antibiotics. 1982;35(8):2100-10.
Aly HA, Hassan MH. Potential testicular toxicity of gentamicin in adult rats. Biochem Biophysical Research Communications. 2018;497(1):362-7.
Karaman M, Budak H, Çiftci M. Amoxicillin and gentamicin antibiotics treatment adversely influence the fertility and morphology through decreasing the Dazl gene expression level and increasing the oxidative stress. Arch Physiol Biochem. 2018: 1-9.
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.
Khaki A, Novin MG, Khaki A, Fathiazad F, Khaberi M, Hossinchi J, et al. Ultra structural study of gentamicin and ofloxacin effect on testis tissue in rats: Light and transmission electron microscopy. African J Pharm Pharmacol. 2009;3(4):105-9.
Nouri M, Khaki A, Fathiazar F, Rashidi MR. The protective effects of carrot seed extract on spermatogenesis and cauda epididymal sperm reserves in gentamicin treated rats. Yakhteh. 2009: 327-331.
Lee V, De Kretser D, Hudson B, Wang C. Variations in serum FSH, LH and testosterone levels in male rats from birth to sexual maturity. Reproduction. 1975;42(1):121-6.
Blanco-Rodriguez J, Martinez-Garcia C. Apoptosis precedes detachment of germ cells from the seminiferous epithelium after hormone suppression by short-term oestradiol treatment of rats. Int J Androl. 1998;21(2):109-15.
Dohle G, Smit M, Weber R. Androgens and male fertility. World J Urol. 2003;21(5):341-5.
Knorr D, Vanha-Perttula T, Lipsett M. Structure and function of rat testis through pubescence. Endocrinology. 1970;86(6):1298-304.
Khaki A, Khaki A, Iraj S, Bazi P, Imani SAM, Kachabi H. Comparative Study of Aminoglycosides (Gentamicin & Streptomycin) and Fluoroquinolone (Ofloxacin) Antibiotics on Testis Tissue in Rats: Light and Transmission Electron Microscopic Study. Pak J Med Sci. 2009;25(4):624-9.
Lenzi A, Gandini L, Lombardo F, Picardo M, Maresca V, Panfili E, et al. Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: from basic to clinic. Contraception. 2002;65(4):301-4.
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 Reviews. 1997;25(2-3):287-98.
Carlier M-B, Rollman B, Van Hoof Fi, Tulkens P. Mechanism of aminoglycoside-induced lysosomal phospholipidosis: in vitro and in vivo studies with gentamicin and amikacin. Biochem Pharmacol. 1982;31(23):3861-70.
