Osuntokun Opeyemi Samson, Olayiwola Gbola, Oladele Ayowole, Ola Idowu, AyokaAbiodun Oludele
Department of Physiological Sciences, Faculty of Basic Medical Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria; Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Osun State University, Osogbo, Nigeria.
Department of Clinical Pharmacy and Pharmacy Administration, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria.
Pathophysiology. 2017 Jun;24(2):63-69. doi: 10.1016/j.pathophys.2017.01.004. Epub 2017 Feb 13.
The effect of chronic administration of gabapentin, carbamazepine or a gabapentin-carbamazepine combination on testicular function in male rats was investigated to determine the effect of combining reduced doses of anti-epileptic drugs on the management of seizures, particularly with respect to the testis sequellae of chronic anti-epileptic administration. Male rats were randomized into four groups (n=10). Each group received daily intraperitoneal (i.p.) injections for 28days as follows: Group I, normal saline 0.1mL/day; Group II, gabapentin (GBP) 16mg/kg/day; Group III, carbamazepine (CBZ) 20mg/kg/day; and Group IV, sub-therapeutic doses of both GBP (8mg/kg) and CBZ (10mg/kg)/day. Twenty-four hours after the last treatment, five rats from each group were sacrificed and the remaining rats were allowed to recover for another four weeks. Sperm characteristics, serum testosterone, and histological integrity of the testis was assessed 24h after treatment and after 28days of drug withdrawal. GBP, CBZ, and GBP-CBZ combination significantly reduced the absolute weight of the testis, epididymis, and seminal vesicle (p<0.05). Moreover, epididymal sperm count and morphology were significantly decreased (p<0.05) in GBP, CBZ, and GBP-CBZ groups. Reduction in serum levels of testosterone for all of the treated groups was statistically significant (p<0.05). The cytoarchitecture of the testicular tissue in the testis of CBZ and GBP-CBZ groups showed disorganization. The altered testicular function were almost restored in GBP treated rats. CBZ and GBP-CBZ combination have delayed but reversible antifertility in the rats. Hence, chronic administration of GBP, CBZ, and GBP-CBZ combination reversibly reduced testicular function in male rats.
研究了长期给予加巴喷丁、卡马西平或加巴喷丁 - 卡马西平组合对雄性大鼠睾丸功能的影响,以确定联合使用低剂量抗癫痫药物对癫痫治疗的效果,特别是关于长期抗癫痫药物治疗对睾丸的后遗症。雄性大鼠被随机分为四组(n = 10)。每组每天腹腔注射28天,具体如下:第一组,每天注射0.1mL生理盐水;第二组,每天注射加巴喷丁(GBP)16mg/kg;第三组,每天注射卡马西平(CBZ)20mg/kg;第四组,每天注射亚治疗剂量的GBP(8mg/kg)和CBZ(10mg/kg)。最后一次治疗24小时后,每组处死5只大鼠,其余大鼠再恢复四周。在治疗后24小时以及停药28天后评估精子特征、血清睾酮水平和睾丸的组织学完整性。GBP、CBZ和GBP - CBZ组合显著降低了睾丸、附睾和精囊的绝对重量(p<0.05)。此外,GBP组、CBZ组和GBP - CBZ组的附睾精子计数和形态显著降低(p<0.05)。所有治疗组的血清睾酮水平降低具有统计学意义(p<0.05)。CBZ组和GBP - CBZ组大鼠睾丸组织的细胞结构显示紊乱。GBP治疗的大鼠中改变的睾丸功能几乎恢复。CBZ和GBP - CBZ组合在大鼠中具有延迟但可逆的抗生育作用。因此,长期给予GBP、CBZ和GBP - CBZ组合可使雄性大鼠的睾丸功能可逆性降低。