Ünal Seyhan Güllen, Take Gülnur, Erdoğan Deniz, Göktas Güleser, Sahin Erhan
Department of Histology and Embryology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
Toxicol Ind Health. 2016 May;32(5):777-90. doi: 10.1177/0748233713512364. Epub 2013 Nov 27.
This study aimed to observe the possible protective effects of resveratrol (RSV) against the damage of di-n-butyl phthalate (DBP) on the testis. The study was conducted in 6 groups of rats with 6 animals in each group aged 20 days. The groups include group 1: control group; group 2: solvent (carboxymethylcellulose (CMC), 10 ml/kg); group 3: 500 mg/kg/day DBP; group 4: 500 mg/kg/day DBP + 20 mg/kg/day RSV; group 5: 1000 mg/kg/day DBP; and group 6: 1000 mg/kg/day DBP + 20 mg/kg/day RSV. Groups were treated by gavage for 30 days. Indirect immunohistochemical staining was performed with c-kit, AT1, and ER-α antibodies. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) method was used for apoptosis. It was found in the DBP-applied groups the C-kit immunostaining, which is parallel to increasing dose, decreased in comparison with the control. C-kit reactivity was similar to that of the control group in the group applied with 500 mg/kg/day + RSV; however, the reactivity was not same in the 1000 mg/kg/day DBP-applied group. It was observed that the reactivity of AT1 increased in the DBP-applied groups. RSV reversed these changes with its protective effects. While there was not much difference between the groups in terms of estrogen receptor reactivity, it was observed that the high dose of DBP reduced the level of estrogen receptor and the resveratrol was not at enough levels in all doses. In TUNEL analysis, high doses of DBP increased the apoptosis in all types of cells; nevertheless, the resveratrol application decreased the apoptosis in the low-level DBP dose. In the statistical analysis, while the length of epithelium and the diameter of seminiferous tubules decreased for all the other groups, it reverted to its original state in the RSV-applied groups. In conclusion, DBP (with increasing dose) administration caused cycle and hormonal changes in testis, resveratrol were recovered the cyclic changes but in hormonal changes, RSV is efficient too but inadequate.
本研究旨在观察白藜芦醇(RSV)对邻苯二甲酸二丁酯(DBP)所致睾丸损伤的可能保护作用。该研究以6组20日龄大鼠进行,每组6只动物。分组包括:第1组:对照组;第2组:溶剂组(羧甲基纤维素(CMC),10 ml/kg);第3组:500 mg/kg/天DBP;第4组:500 mg/kg/天DBP + 20 mg/kg/天RSV;第5组:1000 mg/kg/天DBP;第6组:1000 mg/kg/天DBP + 20 mg/kg/天RSV。各组经灌胃给药30天。用c-kit、AT1和ER-α抗体进行间接免疫组化染色。采用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记(TUNEL)法检测细胞凋亡。结果发现,在应用DBP的各组中,与对照组相比,与剂量增加呈平行关系的C-kit免疫染色减少。在应用500 mg/kg/天 + RSV的组中,C-kit反应性与对照组相似;然而,在应用1000 mg/kg/天DBP的组中,反应性不同。观察到在应用DBP的各组中AT1反应性增加。RSV以其保护作用逆转了这些变化。虽然各组之间雌激素受体反应性差异不大,但观察到高剂量DBP降低了雌激素受体水平,且所有剂量的白藜芦醇水平均不足。在TUNEL分析中,高剂量DBP增加了所有类型细胞的凋亡;然而,应用白藜芦醇减少了低剂量DBP组的凋亡。在统计分析中,虽然所有其他组的上皮长度和生精小管直径减小,但在应用RSV的组中恢复到了原始状态。总之,DBP(剂量增加)给药导致睾丸的周期和激素变化,白藜芦醇恢复了周期变化,但在激素变化方面,RSV也有效但不足。