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-carotene, etc., to reduce the activity of free radical-induced reactions has drawn increasing attention (Chakraborty et al., 1994; McCall, 1999).

In this study we investigated the effect of antioxidant ascorbic acid on semen parameters of male Sprague-Dawley rats treated with anti androgen Bicalutamide.

Materials And Methods

Experimental Animals

Bicalutamide And Ascorbic Acid

Animal Sacrifice And Seminal Fluid Analysis

Statistical Analysis

Results

The results showed significant decrease in mean sperm count from control values of 81.8 ± 1.06 in all the treatment groups; there were similar observed decreases in mean sperm motility.

Figure 1

TABLE 1: Mean sperm count (Millions/ml)

*Significant at p<0.05

S.E.M: Standard Error of Mean

Figure 2

FIGURE 1: Showing percentage Sperm motility of the different groups

There were statistically significant decrease groups in groups B and D. p< 0.05.

Discussion

The result of the sperm counts in millions per milliliters at p<0.05 shows a statistically significant reduction in the count and a concomitant reduction in percentage sperm motility in groups B and D. This result is in consonance with previously reported deleterious effects observed in semen parameters in rats treated with Bicalutamide. Bicalutamide is an endocrine disruptor (Kelce and Wilson, 1997; Jane, 2004) and as has been shown with other endocrine disruptors, it has deleterious effect on reproductive function of male Sprague-Dawley rats. The groups treated with concomitant ascorbic acid administration did not show any statistically significant difference when compared with the control (Table 1 and Figure 1). Ascorbic acid administered as an adjunct modulates the deleterious effects of Bicalutamide. Ascorbic acid, a water soluble vitamin is well known for its anti-oxidant properties (Chakraborty et al., 1994; Glenn et al., 1996; McCall and Balz, 1999;). As an anti-androgen Bicalutamide therapy causes cellular androgen deprivation. It removes the testosterone induced augmentation of basal reactive oxygen species production with resultant diminution of the cellular response against oxidative stress. The diminished production of reactive oxygen species (ROS) ablates or at least diminishes cellular response to oxidative stress which ascorbic acid restores (Winkler 1999; Jehonathan et al., 2007). This has proven beneficial in this experiment. High concentration levels of free radicals are known to be hazardous to living organisms and lead to damage of all major cellular constituents. At moderate concentrations however, ROS play an important role as regulatory mediators in the signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress (Oschsendorf, 1999; Droge, 2002).

Ascorbic acid is also reported to have empirical effects on the reproductive system; it has been shown that ascorbic acid supplement maintains male fertility even when administered empirically (Sapra et al., 1987).

Conclusion

Administration of Ascorbic acid as an adjuvant in anti-androgen therapy would prove beneficial, particularly in the maintenance of semen quality parameters of sperm count and motility. The protective effect of ascorbic acid may be of clinical benefit as an adjunct treatment of males with androgen sensitive tumors on Bicalutamide therapy who may wish to preserve their reproductive function.

Aknowledgement