Abstract
Potential Effect of Botulinum Neurotoxin A in the Treatment of Induced Benign Prostatic Hyperplasia in Male Rats
Author(s): Ghazi Faisal Majid*, Mustafa Ghazi Alabbassi and Israa B. RaofBackground: Researches carried out in humans, dogs, and rats showed that the injection of botulinum neurotoxin type A into the prostate gland reduce the size and other biomarker that indicate botulinum neurotoxin type A as a new promising treatment for benign prostatic hyperplasia.
Aim of the research: The purpose of the study is to evaluate the effects of botulinum neurotoxin type A in the treatment of induced BPH rat model, comparing it with the most powerful standard treatment available composed of alfuzosin and dutasteride (combination of α1 adrenergic antagonist and 5α reductase inhibitor) for BPH rat model and also to describe the mechanism by which botulinum neurotoxin type A effect prostate growth by focusing on acetylcholine-prostate nicotinic receptor signal role in BPH.
Method: Five groups each of them composed of 10 rats. Normal group administered normal saline IP for 42 days. Induction group induced with BPH by testosterone 4 mg/kg/day SC injection for 14 days then administered normal saline IP for 28 days. Conventional treatment group induced BPH by testosterone 4mg/kg/day SC injection for 14 days then administered combination of alfuzosin and dutasteride daily through oral gavage for 28 days. Botulinum group induced BPH by testosterone 4 mg/kg/day SC injection for 14 days, then the injected inside the prostate at day 15 with botulinum neurotoxin type A and left free for 27 days. Nicotine group induced BPH by testosterone for 14 days, then the injected inside the prostate at day 15 with botulinum neurotoxin type A and administered nicotine orally for 27 days. At the end of the experiment rats weighed and sacrificed and blood and prostate samples were collected for PI, CPV, APV determination and sTNFα, sPSA, sCASP3, pTNFα,pPSA and pCASP3 ELISA testing.
Results: Botulinum, conventional treatment and normal groups had a PI (g/100 g) equal to 0.239 ± 0.056, 0.244 ± 0.025 and 0.208 ± 0.045 respectively and showed a significant (P ≤ 0.05) reduced PI when compared with induction and nicotine groups which had PI equal to 0.317 ± 0.053 and 0.338 ± 0.088 respectively. Botulinum, conventional treatment and normal groups had CPV (mm3) equal to 472.6 ± 62, 468 ± 123.4 and 370.1 ± 100.3 respectively and expressed a significant (P ≤ 0.05)reduced CPV in comparison with induction and nicotine groups which possessed CPV equivalent to 997.9 ± 148.6 and 845 ± 177 respectively. Botulinum, conventional treatment and normal groups had a APV (ml) equal to 380 ± 94.8, 385 ± 127 and 330 ± 67.4 in that order and showed a significant (P ≤ 0.05) reduced APV when compared with induction and nicotine groups which had a APV equal to 825 ± 139.9 and 845 ± 177 respectively. Botulinum, conventional treatment and normal groups had a sTNFα (ng/ml) 84.327 ± 28.063, 99.545 ± 27.78 and 78.2 ± 34.195 respectively and pTNFα (ng/ml) equal to 41.272 ± 6.78, 48.763 ± 27.662 and 37.218 ± 6.415 respectively. Induction group and nicotine group possessed a sTNFα equivalent to 139.236 ± 34.691 and 157.836 ± 24.517 respectively and pTNFα equal to 84.054 ± 67.871 and 95.712 ± 47.056 respectively. Botulinum, conventional treatment and normal groups showed a significant (P ≤ 0.05) reduction in both sTNFα and pTNFα in comparison with induction and nicotine groups. Botulinum, normal groups had a sPSA equal to 0.685 ± 0.264 and 0.629 ± 0.126 respectively showed a significant (P ≤ 0.05) reduction in sPSA when compared with induction, nicotine groups which had a sPSA equal to 1.023 ± 0.423 and 1.328 ± 0.356 respectively. Botulinum, normal groups had a pPSA equivalent to 0.339 ± 0.213 and 0.315 ± 0.164 respectively expressed a significant (P ≤ 0.05) reduction on pPSA in comparison with induction and nicotine groups which possessed a pPSA equal to 0.606 ± 0.394 and 0.65 ± 0.24 respectively. Conventional treatment group had a sPSA equal to 0.886 ± 0.188 and pPSA equal to 0.411 ± 0.197 and showed a no significant difference (P>0.05) in both sPSA and pPSA when compared with normal, induction and botulinum groups, on the other hand showed a significant difference with nicotine group. Results showed no significant difference in sCASP3 (P>0.05) between all goups. Botulinum group express a pCASP3 equal to 10.843 ± 7.731 and showed a significant increase (P ≤ 0.05) in PCASP3 when compared with normal, induction, conventional treatment and nicotine groups which had a PCASP3 equal to 2.38 ± 1.627, 2.151 ± 1.582, 3.319 ± 3.504 and 2.15 ± 1.444 respectively. The PPI of BPH of botulinum, conventional treatment and nicotine groups equal to 71.5%, 66.7% and -19.5% respectively.
Conclusion: BTXA intraprostatic injection found to reduce hyperplasia by induction of apoptosis, reduce inflammation and decrease PSA. It also obvious from the results that BTXA as effective as the conventional treatment and have advantage of less side effects and be single injection instead of daily medication. Nicotine administration reverses the effects of Botulinum neurotoxin type A that’s show the central role of nicotinic receptor stimulation in the pathogenesis of BPH.