Research Articles

2019  |  Vol: 5(1)  |  Issue: 1(January-February)  |  https://doi.org/10.31024/ajpp.2019.5.1.1
Evaluation of antifertility potential of ketoconazole and assessment of its reversible effect on concomitant treatment with metformin and Hydroxytyrosol in rats

J. Anbu1*, Shah Akshay Mahendra1, Lakshmi M. Sundar2, Ramya P. S. Reddy1Damodar Nayak1

1Department of Pharmacology,

Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka-560054 India

2Department of Pharmaceutical Chemistry,

Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka-560054 India

*Address for Correspondence

Dr. J. Anbu, Professor

Department of Pharmacology, Faculty of Pharmacy

M.S. Ramaiah University of Applied Sciences, MSR Nagar, Bangalore, Karnataka, India- 560054

Abstract

Objective: In the present study, we aimed to evaluate antifertility potential of Ketoconazole and influence of Metformin in normalization of infertility with the support of strong antioxidant Hydroxytyrosol as a supplementary agent. Materials and Methods: To fix the combinational therapeutic dose the toxicological assessment was done and found to be non-toxic at maximum of 20mg/kg dose level. In the in vivo pharmacological studies, we tested the toxic effect of Ketoconazole alone and its normalization effect in the formulated Ketoconazole and Metformin with Hydroxytyrosol 20mg/ml suspension (KMH) at 5, 10, 20 mg/kg. p.o. on the epididymal spermatozoa. The adult male rats were exposed to KMH for 14 days. The rats (n=6) were grouped as normal control group received 2% CMC alone as vehicle. Second group of animals served as positive control treated with only Ketoconazole as male infertility agent. Third group of rats were administered with KMH for 14days and left untreated for further period of 14 days.

Results: Ketoconazole treatment resulted in a significant decrease in the epididymal sperm count, motility and viability and increased incidence of sperm abnormalities. However, the toxic effect of Ketoconazole was reversible in the KMH group. Thus, the present investigation suggests that the chronic treatment of ketoconazole is capable of inducing male infertility and supplementation with Metformin and Hydroxytyrosol combinational therapy significantly(P<0.01**) helps in regaining the mating behavior, number of spermatozoa in the Cauda epididymis, motility of spermatozoa, weights of testes, epididymides, vas deferens and prostate were normalized. The micro anatomical architecture of male reproductive organs, mating behavior and F1 litter size and other biochemical parameters in this group confirms the reversal effect of fertility with normal reproductive character in the male rats. Conclusion: Based on the results obtained in this study, it is concluded that the combination of Ketoconazole, Metformin and Hydroxytyrosol at the dose level used can be used to induct safe and reversible male infertility.

Keywords: Antifertility, Ketoconazole, Metformin, Hydroxytyrosol, Microanatomical, Cauda epididymis

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