Changes in reproductive organs, semen characteristics and intra-testicular oxidative stress in adult male rats caused by azithromycin

Authors

  • Mossad El-Sayed Department of Pharmacology, Faculty of Veterinary Medicine, Benha University
  • Mohamed Kandiel Department of Theriogenology, Faculty of Veterinary Medicine, Benha University
  • Dalia Ebied El-Nile Company for Pharmaceutical and Chemical Industries

DOI:

https://doi.org/10.14419/ijpt.v5i2.7778

Published:

2017-07-19

Keywords:

Azithromycin, Histopathology, Spermiogram, Testicular Oxidative Stress, Testosterone, Rats.

Abstract

This study aimed to evaluate the numerous azithromycin (as a member of macrolides) effects on the male reproductive organs, spermio-gram, testicular oxidative stress markers of adults’ male albino rats. Azithromycin was administered orally once daily to male rats (200-250 b.wt.) at a dose of 45 mg (therapeutic) or 90 mg/kg b.wt. (double-therapeutic) for three or six days and scarified at the first, thirty and sixty days after the last dose of administration.
A significant decrease as the index weight of the reproductive organs as well as sperm motility, livability and cell concentration, but sperm abnormalities increased at varying times post-treatment with azithromycin administration.
Testosterone hormone level did not vary significantly after azithromycin dosing for three days along the experimental period. However, it differed at the first day after the end of azithromycin dosing for six days.
The intra-testicular oxidative stress alteration mostly occurred at the thirty-day post-treatment in the three- and six-days protocols. In the three-days protocol, there was a significant decrease in malondialdehyde level and superoxide dismutase enzyme activity in a double-therapeutic group. In the six-days regimen, there was an increased activity of catalase enzyme, accompanied with a significant decrease in malondialdehyde levels as well as glutathione peroxidase enzymes.
Double therapeutic dose for six days’ treatment was associated with vascular congestion and perivascular inflammatory cells and ho-mogenous eosinophilic material infiltration into the stroma of testes. The lumen of seminiferous tubules and epididymis showed azoo-spermia.
From these results, it could be concluded that azithromycin administration has hazard effects on male adult’s rats’ fertility governed with the spermiogram, oxidative stress and the histopathological alternations during the post-treatment period.

References

[1] Schlegel PN, Chang TS, Marshal FF. Antibiotics: Potential hazards to male fertility. Fert Ster 1991; 55:235-242 https://doi.org/10.1016/S0015-0282(16)54108-9.

[2] Martinez FJ, Curtis JL, Albert R. Role of macrolide therapy in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease 2008; 3:331-350. https://doi.org/10.2147/COPD.S681.

[3] Cervin A, Wallwork B, Mackayâ€Sim A, Coman WB, Greiff L. Effects of longâ€term clarithromycin treatment on lavageâ€fluid markers of inflammation in chronic rhinosinusitis. Clinical physiology and functional imaging 2009; 29:136-134 https://doi.org/10.1111/j.1475-097X.2008.00848.x.

[4] Bright GM, Nagel AA, Bordner J, Desai KA, Dibrino JN, Nowakowska J, Vincent L, Watrous RM Sciavolino FC, English AR, Retsema JA, Anderson MR, Brennan LA, Borovoy RJ, Cimochowski CR, Faielia JA, Girard AE, Girard D, Herbert C, Manousos M and Mason R. Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a -aza-9a-homoerythromycin A derivatives: a new class of macrolide antibiotics, The azalides. J Antibiot 1988; 41:1029-1047. https://doi.org/10.7164/antibiotics.41.1029.

[5] Retsema J, Girard A, Schelkly W, Manousos M, Anderson M, Borovoy R, Brennan L and Mason R. Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms. Antimicrobial Agents and Chemotherapy 1987; 31:1939-1947. https://doi.org/10.1128/AAC.31.12.1939.

[6] Girard AE, Girard D, English AR, Gootz TD, Cimochowski CR, Faiella JA, Haskell SL and Retsema JA. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), A new macrolide with an extended half-life and excellent tissue distribution. Antimicrob Agents Chemother 1987; 31:1948-1954. https://doi.org/10.1128/AAC.31.12.1948.

[7] Girard AE, Girard D, Retsema JA. Correlation of the extravascular pharmacokinetics of azithromycin with in-vivo efficacy in models of Localized infection. J Antimicrob Chemother 1990; 25(Suppl. A):61-71. https://doi.org/10.1093/jac/25.suppl_A.61.

[8] Paget GE and Barnes JM. Evaluation of drug activities. Pharmacometrics: Vol.1. New York Academic Press, 1964, p. 161.

[9] Clermont Y and Harvey SC. Duration of seminiferous epithelium of normal L- hypophysectomized and hypophysectomized hormone treated albino rats. Endocrinology 1965; 79: 80-88. https://doi.org/10.1210/endo-76-1-80.

[10] Matousek J. Effect on spermatogenesis in guinea pigs, rabbits and sheep after their immunization with sexual fluid of bulls. Journal of Reproduction and Fertility 1969; 19: 63-72. https://doi.org/10.1530/jrf.0.0190063.

[11] Bearden HJ and Fuquary J. Applied Animal Reproduction. Restore Publishing Co. Inc., Reston, Virginia, USA 1980:158-160.

[12] Aebi H. Catalase in vitro. Methods in Enzymology 1984; 105:121-126. https://doi.org/10.1016/S0076-6879(84)05016-3.

[13] Ohkawa H, Ohishi N and Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry1979: 95: 351-358. https://doi.org/10.1016/0003-2697(79)90738-3.

[14] Nishikimi M, Roa NA and Yogi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulphate and molecular oxygen. Biochemical Biophysical Research Communications 1972; 46: 849-854. https://doi.org/10.1016/S0006-291X(72)80218-3.

[15] Paglia DE and Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxide. Journal of laboratory and Clinical Medicine1967; 70:158-169.

[16] Horton R and Tait JF. Androstenedione production and interconversion rates measured in peripheral blood and studies on the possible site of conversion to testosterone. Journal of Clinical Investigation 1966; 45: 301-303. https://doi.org/10.1172/JCI105344.

[17] Banchroft JD, Stevens A and Turner DR. Theory and practice of histological technique Fourth Edition. Churchill Livingstone, New York, London, San Francisco, Tokyo.1996.

[18] Snedecor GW and Cochran WG. Statistical Methods, 6th ed, Iowa Univ Press, Ames, USA. 1982.

[19] Duncan DB. Multiple Range and Multiple F Tests. Biometrics 11:1. Eno, C. F. 1966. Chicken Manure. Fla Agr Exp Sta Circ S-140.1955.

[20] Periti P, Mazzei T, Mini E and Novelli A. Adverse effects of macrolide antibacterial. Drug Saf 1993; 9:346-364. https://doi.org/10.2165/00002018-199309050-00004.

[21] Sikka SC. Testicular toxicology. In Harvey PW, Rush K.C. and Cockburn A. (eds) Endocrine and Hormonal Toxicology. John Wiley and Sons, Chichester; 1999: 99-110.

[22] El-Dakak A. The protective effect of some natural antioxidants against azithromycin induced testicular dysfunction in rats. American International Journal of Contemporary Scientific Research 2015; 2: 39-60

[23] Schramm P, Schopf RE and Wildfeuer A. Josamycin concentration in human ejaculate and its influence on sperm motility-a contribution to antibiotic therapy in andrological patients. Andrologia 1988; 20:521-525. https://doi.org/10.1111/j.1439-0272.1988.tb03137.x.

[24] Schill WB and Przybilla B. Side effects of drugs on male fertility. Z Hautkr 1985; 60:1066, 1069-76, 1079-1082.

[25] Lastikka L, Virsu ML, Halkka O et al. Goniomitosis in rats affected by mycoplasma or macrolides. Med Biol 1976; 54: 146–149.

[26] Folgero BTK, Lindal S, Torbergsen T and Oian P. Mitochondrial disease and reduced sperm motility. Hum Reprod 1993; 8:1863-1868. https://doi.org/10.1093/oxfordjournals.humrep.a137950.

[27] Bodetti TJ, Hengstberger K, Johnston S and Timms P. Evaluation of tetracycline, erythromycin, penicillin and streptomycin for decontamination koala semen contaminated in vitro with chlamydia. Vet Rec 2003; 153:588-591. https://doi.org/10.1136/vr.153.19.588.

[28] Hargreaves CA, Rogers S, Hills F, Rahman F, Howell RJ and Homa ST. Effects of co-trimoxazole, erythromycin, amoxycillin, tetracycline and chloroquine on sperm function in vitro. Human Reproduction 1998; 13:1878–1886. https://doi.org/10.1093/humrep/13.7.1878.

[29] Berndtson WE and Foote RH. Survival and fertility of antibiotic-treated bovine spermatozoa. J Dairy Sci 1976; 59:2130-2133. https://doi.org/10.3168/jds.S0022-0302(76)84498-0.

[30] Baker HW, Straffon WG, McGowan MP, Burger HG, de Kretser DM and Hudson B. A controlled trial of the use of erythromycin for men with asthenospermia. International Journal of Andrology 1984; 7:383-388. https://doi.org/10.1111/j.1365-2605.1984.tb00795.x.

[31] Al-Sultani YKM, Al-Musawi NR and Al-Janaby HS. Effect of ciprofloxacin on spermiogram of infertile patients. Kufa Med J 2000; 3:253-256.

[32] Abd-Allah AR, Aly HA, Mustafa AM, Abdel-Aziz AA and Hamada FM. Adverse testicular effects of some quinolone members in rats. Pharmacol Res 2000; 41: 211-219. https://doi.org/10.1006/phrs.1999.0580.

[33] Khaki A, Ghaffari Novin M, Khaki AA, Fathiazad F, Khaberi M, and Hossinchi J. Ultra-structural study of gentamicin and ofloxacin effect on testis tissue in rats: Light and transmission electron microscopy. African Journal of Pharmacy and Pharmacology 2009; 3:105-109.

[34] Yadav SB, Suryakar AN, Huddedar AD and Shukla PS. Effect of antioxidants and antibiotics on levels of seminal oxidative stress in leukocyte spermic infertile men Indian Journal of Clinical Biochemistry, 2006; 21: 152-156. https://doi.org/10.1007/BF02913085.

[35] Valenzuela A. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 1990; 48: 301-309. https://doi.org/10.1016/0024-3205(91)90550-U.

[36] Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem. 1997; 43:1209-1214.

[37] Chan KM and Decker EA. Endogenous skeletal muscle antioxidants. Crit. Rev. Food Sci. Nutr. 1994; 34: 403–426. https://doi.org/10.1080/10408399409527669.

[38] Olayinka ET and Ore A. Influence of Azithromycin Treatment on Hepatic Lipid Peroxidation and Antioxidant Defense Systems of Rats. British Journal of Pharmaceutical Research 2014; 4: 240-256. https://doi.org/10.9734/BJPR/2014/3853.

[39] Tramer F, Rocco F, Micali F, Sandri G and Panfili E. Antioxidant Systems in Rat Epididymal Spermatozoa. Biol Reprod 1998; 59:753- 758. https://doi.org/10.1095/biolreprod59.4.753.

View Full Article: