Efficacy of enteric-coated sustained-release tadalafil in ameliorating renal fibrosis due to ureteral obstruction in mice
10.3969/j.issn.1000-4718.2024.08.013
- VernacularTitle:他达拉非肠溶缓释新剂型对输尿管梗阻引起的肾纤维化小鼠治疗作用的研究
- Author:
Zhuang LI
1
;
Aolu LIU
;
Limei LI
;
Aini YU
;
Fan LIU
;
Zhenggang ZHAO
;
Zijian Allan ZHAO
;
Yunping MU
;
Fanghong LI
Author Information
1. 广东工业大学生物医药学院,广东 广州 510006
- Keywords:
tadalafil;
enteric-coated sustained-release new dosage form;
renal fibrosis;
unilateral ureteric ob-struction;
collagen deposition;
renal injury
- From:
Chinese Journal of Pathophysiology
2024;40(8):1463-1469
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction(UUO).METHODS:Eight-week-old male C57BL/6J mice were divided into four groups randomly:sham group,UUO group,UUO+new dosage form of tadalafil(1 mg/kg)group and UUO+original patented drug of tadalafil(5 mg/kg)group.Surgery was performed to create a mouse UUO model,and therapeutic drugs were administered intragastrically for 7 d after modeling.A fully automated biochemi-cal analyzer was used to detect serum creatinine(SCr)levels of each group.Through renal histopathological staining(HE staining,Masson trichrome staining,and immunohistochemistry staining)and Western blot,we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice,as well as its effect on the expression and distribution of fibronectin(FN)and α-smooth muscle actin(α-SMA).RESULTS:Compared with sham group,the SCr levels were significantly increased in mice with renal fibrosis,and renal tubules were dilated and in-filtrated with inflammation.Moreover,the expressions of FN and α-SMA were increased significantly(P<0.05).New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis,im-proved the renal tissue structure on the affected side,reduced collagen fiber deposition,and inhibited FN and α-SMA ex-pression(P<0.05).CONCLUSION:Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral ob-struction.New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness.
