Evaluation of the Histomorphometric Evidences of Hydroxyurea-induced Testicular Cytotoxicity in Sprague-Dawley Rat
Hydroxyurea (HDU) is approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell disease who experience recurrent moderate to severe pain. Treatment with HDU is however, associated with known side effects such as cytotoxicity and myelosuppression. In the present study we evaluated the effect of a clinically relevant dose of HDU used in the treatment in sickle cell disease on the seminiferous tubules of rats. Adult male Sprague -Dawley rats were orally treated with 25 mg HDU kg-1 body weight/day for 28 consecutive days. Control rats received the vehicle for HDU which was normal saline 2.5 mL kg-1 body weight. Groups of rats were sacrificed variously on the next day, the 56th and the 112 day after the last dosing with HDU or saline. The testis were recovered, weighed and subjected to histopathology. The gross anatomical parameters assessed included the testicular weights and volumes while stereological parameters estimated includes diameter and cross-sectional area of the seminiferous tubules; number of profiles per unit area and numerical density of seminiferous tubules. The results show that treatment with HDU exhibited significant atrophic degeneration in the seminiferous tubules compared with controls. There was an initial manifestation of progressive worsening of the testicular profiles with passage of time, as the animals sacrificed on day 56 demonstrated greater toxicity than those autopsied a day after day 28. However, the animals sacrificed on day 112 showed some improvement in their testicular profiles, suggesting some degree of self-reversal or recovery of the effect. We conclude that HDU has a deleterious effect on the rat testis even at the clinically relevant dose used in management of sickle cell disease.
Cited References Fulltext