The Protective Role Of Ascorbic Acid Administration On The Bicalutamide Induced Reduction In Semen Quality In The Sprague - Dawley Rat.
A Adeniyi, A Oremosu, O Olabiyi, E Akang, C Noronha, A Okanlawon
ascorbic acid, bicalutamide, semen quality, sprague-dawley rat
A Adeniyi, A Oremosu, O Olabiyi, E Akang, C Noronha, A Okanlawon. The Protective Role Of Ascorbic Acid Administration On The Bicalutamide Induced Reduction In Semen Quality In The Sprague - Dawley Rat.. The Internet Journal of Health. 2009 Volume 12 Number 1.
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.
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
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
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
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
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
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
Thirty-five adult (8-10 weeks old) male Sprague-Dawley rats weighing between 160-180g were used for the experiment. They were procured from the animal house center of the College of Medicine University of Lagos. The animals were randomly divided into seven groups of five rats each. They were housed in well ventilated metal cages in the rat room of the department of Anatomy, College of Medicine, University of Lagos under standard conditions and 12: 12 light: dark photoperiodicity. Ambient temperature was between 28oC – 33oC. The animals had access to rat chow and water
Bicalutamide And Ascorbic Acid
The drugs were purchased from the pharmacy department of the Lagos University teaching hospital. Bicalutamide (Casodex®) was in tablet form; the tablets were crushed and completely dissolved in water.
THE EXPERIMENTAL PROTOCOL IS AS FOLLOWS:
Group A: received 10 mg/kg body weight of Bicalutamide daily for 3 weeks
Group B: was administered 10 mg/kg body weight of Bicalutamide daily for 8 weeks
Group C: control, was given equal volumes of distilled water per kg body weight for 3 and 8 weeks.
Group D: Had 20 mg/kg body weight of Bicalutamide for 3 weeks
Group E: Had 20 mg/kg body weight of Bicalutamide for 8 weeks
Group F: Had 10 mg/kg body weight of Bicalutamide and 200 mg/kg body weight of ascorbic acid for 3 weeks
Group G: Had 20 mg/kg body weight of Bicalutamide and 200 mg/kg body weight ascorbic acid for 8 weeks
The route of administration of test substances in all the rats was by gavage.
Animal Sacrifice And Seminal Fluid Analysis
At the end of the experimental period, the rats were sacrificed by cervical dislocation and at necropsy the cauda epididymides of the rats were removed. Several small cuts were made and then placed in 1 ml of normal saline and spermatozoa allowed swim up and the supernatant analyzed for count and motility studies (Yan
The statistical analysis was carried out using student’s t- test at
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.
S.E.M: Standard Error of Mean
There were statistically significant decrease groups in groups B and D.
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
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
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.
The authors are grateful to the family of Late Samuel Adewale Solarin for funding the procurement of the Bicalutamide (Casodex®) used in the experiments. Furthermore, the use of the animals was approved by the Experimental Ethics Committee on Animals Use of College of Medicine, University of Lagos, Nigeria.