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

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.

The protective potential of ginseng on ciprofloxacin-induced male gonadotoxicity.

“…Also, Panax ginseng increases spermatogonia and primary and secondary spermatocytes (Sanad et al, 2021b). Ginseng potentially protects against immobilization stress-induced testicular damage and fertility factors in rats (Lee et al, 2019) Our result also showed decreasing in testosterone hormone levels and increasing in FSH and LH hormones in groups 1 and 2, which received Ciprofloxacin only, parallel to previous findings which reported that Ciprofloxacin caused impairment of Leydig cells and Sertoli cells that led to decrease testosterone level (Mokhimar et al, 2020;Zobeiri et al, 2013) but in groups 3,4and 5 which received Ginseng or vitamin-E along with Ciprofloxacin, the levels of testosterone, FSH and LH have been restored to the normal levels meaning that testicular function has been reserved. In agreement with our findings, treatment with Ginseng at 100 mg and 200 mg/kg returned FSH, LH, and testosterone to their average level (Ismail and El-Nahari, 2009).…”

“…Additionally, we co-administered vitamin E beside the high-dose Ciprofloxacin to another group as a reference antioxidant. The standard dose is calculated as the average dosing of body weight-based and body surface area-based dosing (Mokhimar et al, 2020). Two sacrifice days have been placed, the first was on day 15 to evaluate the acute effects, and the second was on day 60 from the first day of treatment, to follow the sperm cycle from the start of spermatogenesis to sperm maturation (Mahmoudi et al, 2018).…”

“…Ciprofloxacin significantly impairs both testicular function and structure in rats (Abd-Allah et al, 2000), reduces sperm count, motility, and daily sperm production in rats, and adversely affects male fertility (Xie et al, 2019). Oxidative stress is one of the most accused of causing infertility (Mokhimar et al, 2020), hypothesizing that Ginseng is a proven potent antioxidant and might protect from the adverse effects of Ciprofloxacin. Ginseng is always referred to be the King of all herbs and is used to treat sexual dysfunction also enhancing sexual behavior (Leung and Wong, 2013).…”

Antibiotic toxicity on human spermatozoa assessed using the sperm DNA fragmentation dynamic assay

“…Mature spermatozoa obtained after intense and long treatment schedules were generally affected in terms of ejaculate concentration, motility, viability and morphology. These general findings have been reported with all the three antibiotics, ciprofloxacin (Abd et al, 2018;Mokhimar et al, 2020), doxycycline (Elzeinová et al, 2013) and ampicillin (Gupta et al, 2013;Raji et al, 2006). Alterations observed in spermatozoa obtained from in vivo studies are likely to be derived from direct or indirect effects on spermatogonia and/or spermatids in the testis or during epididymal maturation and not a consequence of a direct effect of the antibiotic on the mature gamete.…”

"Evaluation of Chronic Administration of the Concomitant Combination of Artemether- Lumefantrine and Ciprofloxacin on Reproductive Hormones and Prostate Specific Antigen of Adult Male Wistar Rats"

“…In most African countries (Nigeria inclusive), Artemether-lumenfantrine are readily obtainable over the counter, encouraging its use without proper parasitological diagnosis, especially in the poor rural communities The spread of the corona virus (COVID-19) has also led to the increase in the purchase of this anti-malarial drug because of the similarities in the symptoms experienced in patients that are infected with malaria parasite and the corona virus; these symptoms may include headache and fatigue. Ciprofloxacin, on the other hand, belongs to the second generation of fluoroquinolone antibiotics (Mokhimar, et al [5]) with the chemical name cyclopropyl-6-fluoro-4oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid (Jawad,et al [6]). It is used for the treatment of bacterial infections such as skin, bone, and joint infections, urinary tracts infections, prostatitis, typhoid fever, sexually transmitted infections, salmonellosis and others (Thai et al, 2020).…”