Attenuation of ifosfamide adverse effect on leydig, sertoli and spermatogonia cells of ram testis by liposome technique in vitro

Abstract EN

Male infertility is a broad phenomenon adverse effect of the chemotherapeutic drug ifosfamide.

Present warning proposes that the ifosfamide prodrug and their metabolite may contribute to this testicular cell toxicity.

The present experimental study modified ifosfamide dosage form via liposome encapsulation inspected the special effects of ifosfamide and liposome carrying ifosfamide (small and uni/bi-lamellar) on certain isolated testicular cells; Leydig, Sertoli, and spermatogonia in primary culture.

The three cells were isolated in percoll gradient density separation technique from 10 rams and inoculated in separately in LH, FSH and testosterone under growth factor trigger exposed to ifosfamide formulas.

The ability of the gonads-protectant cells medication liposomal entrapment ifosfamide to prevent ifosfamide-induced testicular cell injury was also assessed and prevented liberation potent metabolite of ifosfamide via trapping harmful metabolite that due to the Ifosfamide liposomal entrapped size ranged between 60-110 nm, the small size of liposome prolong t½ life and delay liberation and act as an additional compartment and prevent entry to the secondary targeted cells.

Ifosfamide (300, 600, 1200, 2400 and 3600 µM) were produced dose-dependent drops viability and growth behavior, mitochondrial integrity and ATP levels, cell number and Membrane integrity, COMET DNA analysis, phagocytosis property of Sertoli cell and Leydig cell testosterone concentration, verified the IC50s.

The conclusion was exposure of the isolated cells of ram testis to liposome carrying ifosfamide protected cell via shield or delay of time exposed to harmful of unwanted effect of ifosfamide anticancer drug of all cell types, whereas, the ifosfamide produce decrease proliferative cell viability and demand energetic of cell supplier and function of certain cells as well as upset of DNA properties.

This promotes an efficacious manner of augmented safer use of ifosfamide as a preliminary study