Aboulhoda Basma Emad, Ali Eid Nassar
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt.
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt.
Acta Histochem. 2018 Apr;120(3):269-281. doi: 10.1016/j.acthis.2018.02.008. Epub 2018 Feb 26.
Despite enormous progresses in understanding pathophysiology of the lower urinary tract, antimuscarinics remain the chief clinically well-established approach for improving symptoms of overactive bladder (OAB). Dry mouth on the other hand remains one of the most untolerated systemic side effects of these drugs that limits their uses and results in high discontinuation rate. Three novel drugs have been recently approved by US Food and Drug Administration for treatment of OAB: trospium, darifenacin, and solifenacin.
This study has been conducted to provide clear head to head comparative studying of histological and ultrastructural effect of those newly emerging drugs on parotid and submandibular salivary glands and to demonstrate the differential expression of CXCL10 to make a cogent structural and molecular assessment of the relative tolerability of these drugs and the potential mechanisms of occurrence of dry mouth.
Fifty male Sprague Dawley rats were equally divided into five groups: Group I (control), Group II (oxybutynin-treated), Group III (trospium-treated), Group IV (darifenacin-treated) and Group V (solifenacin-treated). Histological and ultrastructural studies were performed on parotid and submandibular glands. Measurement of salivary flow, PCR analysis and immunohistochemical assessment of CXCL10 expression have been carried-out.
Muscarinic receptor antagonists led to various histological, morphometric and ultrastructural changes together with diminished salivary secretion and up-regulation of CXCL10 expression with the mildest alterations observed with solifenacin.
Solifenacin has shown the least adverse effects to salivary glands. CXCL10 is involved in degenerative changes of salivary glands induced by muscarinic antagonists.
尽管在理解下尿路病理生理学方面取得了巨大进展，但抗毒蕈碱药物仍然是临床上改善膀胱过度活动症（OAB）症状的主要成熟方法。另一方面，口干仍然是这些药物最难以耐受的全身副作用之一，这限制了它们的使用，并导致高停药率。美国食品药品监督管理局最近批准了三种新药用于治疗OAB：曲司氯铵、达非那新和索利那新。
本研究旨在对这些新出现的药物对腮腺和颌下唾液腺的组织学和超微结构影响进行清晰的直接比较研究，并证明CXCL10的差异表达，以便对这些药物的相对耐受性及其口干发生的潜在机制进行有说服力的结构和分子评估。
将50只雄性Sprague Dawley大鼠平均分为五组：第一组（对照组）、第二组（奥昔布宁治疗组）、第三组（曲司氯铵治疗组）、第四组（达非那新治疗组）和第五组（索利那新治疗组）。对腮腺和颌下腺进行组织学和超微结构研究。进行唾液流量测量、PCR分析以及CXCL10表达的免疫组织化学评估。
毒蕈碱受体拮抗剂导致各种组织学、形态学和超微结构变化，同时唾液分泌减少，CXCL10表达上调，索利那新引起的变化最为轻微。
索利那新对唾液腺的不良反应最小。CXCL10参与了毒蕈碱拮抗剂诱导的唾液腺退行性变化。
