The Protective Role Of Ascorbic Acid Administration On The Bicalutamide Induced Reduction In Semen Quality In The Sprague - Dawley Rat.

摘要

Antineoplastic drugs used in the treatment of testicular carcinoma have been reported to have deleterious effects on the fertility potentials in affected males. The mechanism of damage involves the generation of free radicals.We evaluated the effect of using an antioxidant ascorbic acid as an adjuvant treatment with Bicalutamide on the androgen sensitive organs of the male Sprague-Dawley rats.Thirty-five adult male Sprague-Dawley rats weighing between 160-180 g were used for the experiment. The animals were randomly selected and divided into seven groups of five rats each. They were given 10 mg/kg or 20 mg/kg body weight of Bicalutamide and 200 mg/kg of Ascorbic acid for three and eight weeks. The animals were sacrificed and the cauda epididymides excised for sperm count and sperm motility analysis.There was observed decrease in semen quality with Bicalutamide that was attenuated by ascorbic acid co-administration. The concomitant administration of ascorbic acid has a protective role on reproductive function in males on Bicalutamide therapy. Introduction Bicalutamide is used for the treatment of prostatic and testicular cancers. These two forms of androgen specific cancers have an increasing incidence among the adult male populace (Potosky et al., 1995; Hans et al., 1996; Huvghe et al., 2003). Drugs used in chemotherapy of these malignancies adversely affects the reproductive function and may lead to infertility where there is still the desire to procreate (Robbins et al., 1998). Testicular cancer affects the reproductive age group with a peak age of incidence between 20 – 34 years (Huvghe et al., 2003). Though the incidence of prostatic carcinoma varies significantly across ethnic groups, peoples of African descent are at the highest risk (Alice et al., 1995; Parkin et al., 1999). The male reproductive organ malignancies are androgen sensitive having androgen receptors on their cellular membrane surfaces and therefore can be controlled or treated by the administration of anti androgens (Olea et al., 1990; Naohide et al., 1999).In Nigeria there is a burden of androgen sensitive tumours particularly that of the prostate. The incidence of prostatic carcinoma has been reported in literature to be on the increase (Ogunbiyi and Shittu, 1999; Ekwere and Egbe 2002). Some authors have reported that prostate cancer is the most commonly diagnosed cancer among male Nigerians (Ann and Susan, 2001). The incidence of testicular cancer on the other hand remains low in Nigeria (Magoha, 1995; Izegbu et al., 2005); the early age of onset however raises concern about future reproductive potentials of those affected (Stone et al., 2005).Infertility is an important medical problem of great social and cultural dimensions in Sub Saharan Africa, with several figures reported in literature for the Nigerian population (John and Pat, 1987; Robert et al., 1993).Anti-androgens either from the environment or iatrogenically administered are endocrine disruptors (Kelce and Wilson 1997; Jane, 2004) have deleterious effect on male reproductive function (Rex, 1998; Gray et al., 2001). Bicalutamide is an anti-androgen used in the chemotherapy of androgen sensitive tumours (Michael, 2002). The mode of action is by preventing testosterone from binding to the androgen receptors on the prostate and testicular cancer cells. It therefore starves the cancer cell of testosterone, which prevents their growth. Eventually the prostate and the testicular tumor will shrink (Amory, 2007). With the benefit of slowing down the tumor growth, it has also been implicated in the development of male infertility among those on treatment with the drug (Amory, 2007). Use of Antioxidants as agents to scavenge free radicals and reducing oxidative stress in reproductive organs is justifiable as increased oxidative stress has been shown to impair male reproductive function (Sikka et al., 1995; Sharma et al., 2001). The potential role of antioxidants, such as ascorbic acid, tocopherol, B-ca