Efeitos da associação de beta-glucana e itraconazol sobre a fertilidade de ratos Wistar machos / Effects of the Association of Beta-glucan and Itraconazole on Fertility of Male Wistar Rats

ABSTRACT

Background: In recent years, the number of patients with systemic fungal infections requiring antifungal therapy has increased. As a consequence, antimicrobial resistance to conventional treatment is frequently reported. Due to this reason, new therapies emerge, including the combination of beta (1-3) glucan and itraconazole. However, the reproductive and fertility effects of this association were not known. So, the aim of this study was to identify the effects of the combination of itraconazole and beta (1-3) glucan, extracted from Saccharomyces cerevisiae, on male rats fertility. Materials, Methods & Results: Sixty male Wistar rats with 120-days-old were used. The experimental protocol was approved by Ethics Committee on Animal Use of the Federal University of Rio Grande do Sul (protocol CEUA/UFRGS no. 19452/2010). The animals were placed into six groups (n = 10 animals / group) as following Negative Control group - treated daily with the volume corresponding to 10 mL.kg-¹ of sterile distilled water orally and 0.25 mL of sterile normal saline (NaCl 0.9 %) subcutaneously weekly; Itraconazole (IT) group - treated daily with itraconazole solution at a dose of 10 mg.kg-¹ orally and 0.25 mL of sterile 0.9% NaCl subcutaneously weekly; Beta group - treated daily with the volume corresponding to 10 mL.kg-¹ of sterile distilled water orally and 0.5 mg of beta (1-3) glucan subcutaneously weekly; Therapeutic Dose (TD) group - daily treated with itraconazole at a dose of 10 mg.kg-¹ orally and 0.5 mg of ß (1-3) glucan subcutaneously weekly; TD5x - treated daily with itraconazole at a dose of 50 mg.kg-¹ orally and 0.5 mg of beta (1-3 ) glucan subcutaneously weekly; TD10x - daily treated with itraconazole at a dose of 100 mg.kg-¹ orally and 0.5 mg of beta (1-3) glucan subcutaneously weekly. The rats were treated for 91 consecutive days. Individual body mass, organs relative mass and histopathology, number of sperm in the cauda epididymis, daily spermatozoal production, sperm parameters, sperm morphology, serum testosterone concentration and reproductive rates were evaluated. Significant differences were observed in daily spermatozoal production, sperm morphology, serum concentration of testosterone, mating rate and birth rate, with lower results in the TD5x and TD10x groups. Discussion: The systemic toxicity indicators, as body mass variation, water intake and clinical signs, as well as organ histology suggest that systemic toxicity in these animals did not occur. The decrease in serum testosterone concentrations in elevated doses of itraconazole associated with beta (1-3) glucan must be involved in decrease of sperm parameters and in sexual behavior and consequently, in the reproductive rates. Changes in sperm morphology, mainly found in sperm head, indicate sperm immaturity, preamature spermiation, abnormal or degenerate acrosome. Based on these results, it is concluded that beta (1-3) glucan and itraconazole did not affect the male rats reproductive variables when used in therapeutic doses alone or in combination, however these variables were altered with higher doses of itraconazole in the association. These data, added to the absence of histopathological damage of the testes suggest functional effect on male fertility. Caution is advised in the use of high doses of itraconazole with or without beta (1-3) glucan in males, especially in prolonged therapy.