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

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.

Retrospective assessment of the treatment of sporotrichosis in cats and dogs using itraconazole

Background: Cases of sporotrichosis in male and female cats and dogs of different ages with cutaneous sporotrichosis that were treated at the dermatology service of a teaching veterinary hospital and orally administered itraconazole (ITC) were retrospectively characterized by reviewing the clinical records corresponding to a 19-year period (1993-2011). The aim of the present study was to analyze regarding clinical cure, side effects, length of treatment and relapse using ITC in the treatment of cutaneous sporotrichosis in cats and dogs. Materials, Methods & Results: From the assessed case series, 20 animals were selected, of which 17 (85.0%) were cats and three (15.0%) were dogs; the animals were mostly males (80.0%) and of ill-defined breeds (75.0%). Cases of sporotrichosis in male and female cats and dogs of different ages that were treated at the dermatology service of a teaching veterinary hospital and orally administered ITC (10 mg/kg) once a day. The percentage of full remission of the treated cases, regardless of their clinical form, was 100%, and no systemic or tegumentary side effects were found in the assessed animals. The average duration of treatment was 3.4 months in cats and 11.3 months in dogs, whereas the maximum duration of treatment required to resolve the clinical condition in the assessed case series of cats and dogs was 16 months, regardless of the animal species. Relapses occurred in 15.0% (one cat and two dogs) of the cases treated with the investigated antifungal agent. Discussion: The remarkable difference in the average duration of therapy required to achieve clinical cure between cats and dogs might be related to the fact that most of the cases of feline sporotrichosis were of the localized cutaneous form (82.3%). Conversely, the three cases of canine sporotrichosis were of the disseminated cutaneous form, which may have delayed the success of treatment. Clinically manifested systemic or tegumentary side effects were not reported by the pet owners or were detected by clinical examination of the animals that were subjected to treatment with ITC in the present study, which agrees with previous reports. However, given the retrospective character of this research complementary laboratory exams are lacking and thus it cannot be asserted that alterations do not exist. Therapeutic failure was not observed with the use of ITC in the investigated cases of canine and feline sporotrichosis. Clinical relapse occurred in two dogs and one cat, all of which exhibited the disseminated cutaneous form, which might have predisposed them to clinical recrudescence. In addition, the evident difference in the percentage of relapse between the two species might be correlated with the higher prevalence of the disseminated cutaneous form among the investigated dogs (100%) compared with the cats (40%). Of the animals that exhibited relapse, one dog had been treated with topical corticoids for the previous three months. According to the literature, glucocorticoids and other immunosuppressants are contraindicated in dogs and cats with sporotrichosis. The cat, in turn, exhibited respiratory disease complex in addition to sporotrichosis, which might be related to the clinical relapse. In conclusion, ITC is efficacious in the treatment of sporotrichosis in cats and dogs and does not induce apparent side effects.