The effects of imatinib on the testicular histology in male rats administered at peripubertal period

الملخص EN

Objective : Male and female gonadal toxicity are common complications of modern anti-cancer treatments.

Although effective cancer therapy, and where possible cure, are of paramount importance, infertility and hypogonadism can be a source of considerable distress.

There is a paucity of studies on the effect of imatinib on the histological parameters of the testes of rats.

The aim of this study was to evaluate the shortterm effects of peri-pubertal administration of a low dose, clinically non-relevant high dose of imatinib and its repercussions in adulthood in comparison with that of control.

Methods : This experimental study was performed over a period of four months starting from the 10th march 2013 to the 10th July 2013 and was conducted on male Albino rats purchased from Animal Houses of both Mosul Medical College, and Veterinary College, University of Mosul, Mosul, Northern Iraq.

Animals were randomly assigned to the experimental groups.

The first experiment includes 40-45 days aged rats who administered orally daily dose of 75 mg / kg of imatinib mesylate (Glivec® ; Novartis) purchased from Ibn-Sena Teaching Hospital, Mosul, or bought from some private pharmacies for 30 days with age matched control who administered distilled water.

The second experiment includes 40-45 days aged rats who administered daily dose of 200 mg / kg orally with age matched control who administered distilled water.

Animals in each experiment were euthanized with ether 24 hours after the final dose was given, respectively, at the end of treatment (short-term evaluation) and after the recovery period (long-term evaluation), testes of rats from each experimental group were obtained at laboratory of postgraduate studies of Department of Anatomy, Histology and Embryology in Mosul College of Medicine.

The tissues were embedded in paraffin and stained with hematoxylin-eosin, PAS-Harris (PAS-H) stain.

The evaluation was blinded to treatment and any data.

Testes from the control and treated animals are analyzed for any disorganization of cytoarchitecture of seminiferous tubules, the presence of vacuoles, gaps and abnormal cells in the seminiferous epithelium and sloughing, degeneration of seminiferous epithelium and oedema in the interstitial spaces.

Johnsen’ scores were used to evaluate the spermatogenesis in all groups.

The photomicrographs were taken.

Results : The light microscopic examination of the testicular sections obtained from of the control group showed a normal organized appearance of the seminiferous epithelium with intact cytoarchitecture of the testes.

Histological analysis of seminiferous tubules in imatinib-treated rats showed that the most striking features are disorganization of the seminiferous tubules, interstitial oedema, sloughing of the epithelium, and detachment of sertoli cells toward the lumen.

This study revealed that there are different alterations in the testicular histology in the imatinib-treated rats, however these changes were focal, scattered and showed interindividual variability.

In addition, this study showed that the testicular injuries were more pronounced in imatinib-treated with high dose group compared to that of imatinib-treated with low dose group.

Sections obtained from the rats that euthanized after the recovery period demonstrated a better organization of the seminiferous tubules in both low and high dose groups.

Histological assessment demonstrated that both imatinib-treated rats (low dose-IML, or high dose- IMH) presented decreased Johnsen’ scores in relation to control animals, indicating that imatinib induced toxic effects in testis, however, animals euthanized after the recovery period showed better Johnsen’ scores.

Conclusions : Imatinib does affect the histopathology of rat testis significantly at low dose, or at high dose, but this effect is reversible, to some extent, once the drug is withdrawn.

This finding may help the clinicians to plan and address the fertility related issues in young patients of reproductive age who are being treated with imatinib for gastrointestinal tumors and chronic myeloid leukemia.