Bayram Ali, Kaya Altan, Akay Ebru, Hıra İbrahim, Özcan İbrahim
Department of ENT, Kayseri Training and Research Hospital, Kayseri, Turkey.
Department of ENT, Kayseri Training and Research Hospital, Kayseri, Turkey.
Int J Pediatr Otorhinolaryngol. 2017 Mar;94:1-7. doi: 10.1016/j.ijporl.2017.01.005. Epub 2017 Jan 5.
The aim of the present study was to investigate the protective effect of tetramethylpyrazine (TMP) on cisplatin-induced ototoxicity in rats.
Forty healthy, female, 24-week-old, Sprague-Dawley rats (n = 40) were randomly assigned to four groups as follows: group one (n = 10) received intraperitoneal (i.p.) physiological saline at daily doses of 3 mg/kg for seven days; group two (n = 10) received a single dose of i.p. 15 mg/kg cisplatin; group three (n = 10) received i.p. 140 mg/kg TMP daily for seven days plus a single dose of i.p. 15 mg/kg cisplatin on the fourth day; group four (n = 10) received i.p. 140 mg/kg TMP daily for seven days. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements were obtained from the animals (40 rats, 80 ears) under general anesthesia before and after drug administration. The temporal bulla of animals were bilaterally removed for immunohistopathological examination.
In group two, DPOAE and ABR values were significantly deteriorated after drug administration, whereas there was no statistically significant difference between the pre- and posttreatment DPOAE and ABR values for all frequencies for groups one, three and four. The mean scores for external ciliated cells (ECCs), stria vascularis (SV) and spiral ganglion (SG) injuries in hematoxylin and eosin (H&E) staining, and also caspase-3 immunoreactivity were significantly higher in group two than in the other groups.
In the present study, the protective effect of TMP on cisplatin ototoxicity was demonstrated through studies of electrophysiology and immunohistopathology. Co-administration of TMP may have potential protective effects against cisplatin-induced ototoxicity.
本研究旨在探讨川芎嗪(TMP)对顺铂诱导的大鼠耳毒性的保护作用。
将40只健康的24周龄雌性Sprague-Dawley大鼠(n = 40)随机分为四组,如下:第一组(n = 10)每天腹腔注射(i.p.)3 mg/kg生理盐水,共7天;第二组(n = 10)单次腹腔注射15 mg/kg顺铂;第三组(n = 10)每天腹腔注射140 mg/kg TMP,共7天,并在第4天单次腹腔注射15 mg/kg顺铂;第四组(n = 10)每天腹腔注射140 mg/kg TMP,共7天。在给药前后,对动物(40只大鼠,80只耳朵)进行全身麻醉,测量听觉脑干反应(ABR)和畸变产物耳声发射(DPOAE)。双侧切除动物的颞骨泡进行免疫组织病理学检查。
第二组给药后DPOAE和ABR值显著恶化,而第一组、第三组和第四组所有频率的给药前和给药后DPOAE和ABR值之间无统计学显著差异。苏木精-伊红(H&E)染色中,第二组外毛细胞(ECCs)、血管纹(SV)和螺旋神经节(SG)损伤的平均评分以及半胱天冬酶-3免疫反应性均显著高于其他组。
在本研究中,通过电生理学和免疫组织病理学研究证明了TMP对顺铂耳毒性的保护作用。TMP联合给药可能对顺铂诱导的耳毒性具有潜在的保护作用。